ADAM12 polymorphisms may be associated with the risk of knee osteoarthritis (KOA), but currently available evidence remains controversial. We performed this meta-analysis to confirm whether ADAM12 polymorphisms were associated with susceptibility of KOA. A comprehensive literature search in PubMed, EMBASE, and ISI Web of Science was conducted to identify observational studies assessing the association between ADAM12 polymorphisms and susceptibility of KOA. The strength of association was indicated as odds ratio (OR) and the corresponding 95% confidence interval (95%CI). Four types of genetic model  were evaluated for each included study. Subgroup analysis by ethnicity was performed. Seven case-control studies comprising a total of 3512 KOA patients and 5405 healthy controls were included in the meta-analysis. A significant association between rs1871054 and increased KOA risk was found in each genetic model. No significant association was found between KOA and rs3740199, rs1044122, or rs1278279 in any genetic model. Based on the findings of our study, there was a modest but statistically significant association between rs1871054 and risk of KOA in Asian population, while other polymorphisms  in ADAM12 were not associated with KOA in any population.  Osteoarthritis (OA) is the most common chronic and progressive musculoskeletal disease of the elderly all around the world and has been identified in all ages. It is characterized by synovitis, thickening of the joint capsule, progressive degradation of articular cartilage, joint space narrowing, osteophyte formation, and subchondral sclerosis, resulting in chronic joint pain and loss of function of the elderly individuals , 2. The ADAM , a kind of type-I transmembrane and soluble glycoproteins, is involved in the process of signal transduction, cell adhesion, migration, and proteolysis –7. As onThe single-nucleotide polymorphisms (SNPs) within the coding region can alter the amino acid sequence of a protein and influence the function of the corresponding protein. The association of ADAM12 SNPs with the susceptibility to the KOA could provide a new direction in KOA research. Although several studies have suggested that ADAM12 SNPs can influence the susceptibility to knee osteoarthritis but no consensus have been achieved. To our knowledge, no meta-analysis has been carried out to assess the correlation between ADAM12 polymorphisms and susceptibility to KOA. Therefore, we conducted this meta-analysis aiming to assess the association between the ADAM12 SNPs and KOA.This meta-analysis was performed complying with the PRISMA guideline .Eligible studies were retrieved by searching PubMed, EMBASE, and ISI Web of Science. All the online databases were searched up to October 2016 without language restriction. A combination of Medical Subject Heading (MeSH) and free text words was used: (osteoarthritis or osteoarthrosis or osteoarthritides or “Osteoarthritis” [Mesh]) and  and . In addition, we screened the reference lists of relevant reviews to avoid missing eligible studies.Data were collected from published articles, and conference and meeting abstracts were consequently excluded. The studies were included only if they met the following criteria: (1) case-control or cohort studies investigating the association between ADAM12 polymorphism and KOA; (2) KOA should be diagnosed according to the American College of Rheumatology criteria, imaging records or total knee replacement due to primary KOA; (3) healthy controls were required to have no symptoms or signs of KOA, and the genotype distribution of control population should meet the Hardy-Weinberg equilibrium (HWE); (4) included studies should provide odds ratio (OR) and the associated 95% confidence interval (95% CI) or detailed information about genotype frequency. If studies with overlapping population were identified, the most complete one was included in our meta-analysis.Two investigators (Z. Lv and S. Liang) screened each article independently and were blinded to the results of the other reviewer. Two reviewers performed a stringent screening to determine eligible studies independently based on the predesigned inclusion criteria. Data were extracted independently by two reviewers from these selected articles using a standardized collection form, which included first author, country, year of the publication, study design, ethnicity, sample sizes, genotyping in case and control groups, and HWE of control groups. Any disagreement between the two reviewers was resolved through discussion until a consensus was reached. The third review author (A. Chen) was consulted if a consensus could not be reached.The Newcastle-Ottawa Scale (NOS)  for the 2 test was applied for the HWE. The OR of ADAM12 polymorphisms  and OA risk was evaluated for each study, and the strength of association was indicated as OR and the corresponding 95% CI. The additive model was selected as the primary genetic model because it is a robust screen of a variety of other genetic models. Additionally, we determined the association for other possible genetic models: dominant model, recessive model, and allele model. Heterogeneity among studies was estimated using a Q-test and the Higgins I2 test (P > 0.1 and I2 < 50% indicate acceptable heterogeneity). We combined the OR of each study using fixed-effect model if there was no evident between-study heterogeneity across the eligible comparisons. Otherwise, a random-effect model was employed.For the observed genotype frequencies in control group of each included study, ChiP < 0.05.To evaluate the ethnicity-specific effect on the association between ADAM12 polymorphisms and OA risk, subgroup analysis by ethnicity (Asian/Caucasian) was subsequently performed. Begg's rank correlation test and Egger's linear regression test using Stata version 12.0  were used to assess the publication bias if the number of included studies were larger than five. Publication bias was considered present with The literature selection process was presented in Seven case-control studies , 26–31 iThe NOS based on eight items was employed to assess the methodological quality of included studies. The OA cases were diagnosed according to ACR criteria or radiographical examination, and patients that have underwent total knee replacement were also included. However, representativeness of cases in our selected studies was not sufficient because only one study  recruiteI2 = 80%), dominant model , recessive model , and allele model . The polymorphisms rs3740199, rs1044122, and rs1278279 were found with no statistical association with KOA risk no matter for which genetic model.The meta-analysis findings of the association between ADAM12 SNPs and KOA risk were presented in Figures I2 = 0%), dominant model , recessive model , and allele model , but not among Caucasian populations.Subgroup analysis by ethnicity was undertaken to determine whether there was a population-dependent effect on the association between ADAM12 SNP and KOA risk. There was no significant association between polymorphisms rs3740199, rs1044122, rs1278279, and OA risk in all populations. In subgroup analysis based on ethnicity, no statistically significant association was found between rs3740199, rs1044122, rs1278279, and OA risk in either Caucasian or Asian populations. With regard to rs1871054, subgroup analysis by ethnicity revealed that rs1871054 was significantly associated with OA risk among Asian populations: additive model  and Egger's test  showed no significant publication bias.Publication bias was only assessed in polymorphism rs3740199 because the number of included studies was greater than five. Begg's test (additive model: In this meta-analysis we collected seven case-control studies with a total of 3512 KOA patients and 5405 healthy controls, and no restriction on ethnicity and language was imposed. Meanwhile, we performed subgroup analyses to identify population-dependent effect on the association between ADAM12 SNPs and KOA risk. The analysis results of this study indicated a modest but statistically significant association between rs1871054 in ADAM12 and KOA in Asian population but not in Caucasian population. In addition, no significant correlation was found between risk of KOA and rs3740199, rs1044122, or rs1278279 in any population. No evidence was found for publication bias in the meta-analysis for rs1871054 in any genetic model. But, due to the limited number of included studies, funnel plots were not generated for meta-analyses of rs3740199, rs1044122, and rs1278279.2+ dependent metalloproteinase superfamily that have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions [ADAM12, located on chromosome 10q26.2, is a member of the Znractions , 33, celractions , and extractions , which mractions . Thereforactions , which aractions . These eADAM12 gene contains multiple SNPs including rs1871054, rs3740199, rs1044122, and rs1278279. As indicated above, only SNP rs1871054 was confirmed to be associated with a modestly increased risk of KOA in Asian but not Caucasian population. The pooled ORs for additive model contrast, dominant model contrast, recessive model contrast, and allelic contrast all suggested that rs1871054 was associated with an increased risk for KOA. When we restricted the ethnicity to Asian ethnicity, the between-study heterogeneity was low in any genetic model, suggesting that ethnicity might be one of the potential sources of heterogeneity among studies. And the difference of genetic effects between Caucasian and Asian populations may be the outcomes of gene-environment or gene-gene interactions, suggesting that the genetic effect of rs1871054 polymorphisms is stronger in Asia than in Caucasian population. Additionally, different criteria were used to define respective cases, which could also increase the heterogeneity in different ethnic populations.Several potential limitations in our meta-analysis should not be ignored. Firstly, only seven case-control studies were included in this meta-analysis. The sample size was not large enough to exactly validate the correlation between the ADAM12 polymorphisms and susceptibility to KOA. Therefore, more studies with larger sample sizes are required, so as to guarantee the stability and reliability of the meta-analysis. Secondly, the association between SNPs in ADAM12 and susceptibility to KOA may be affected by other confounding factors, such as age, gender, and BMI. We are unable to perform further stratified analysis due to the incomplete raw data. For instance, KOA is known to be more prevalent in females than in males, and future studies should provide detailed allele frequencies and genotypes in both genders. Thirdly, KOA is associated with both genic and environmental risk factors, including body weight, hormonal status, trauma, family history, and selected activation. But the studies included in this meta-analysis did not control for these mixed factors.In conclusion, our meta-analysis suggested that ADAM12 rs1871054 polymorphism is associated with the susceptibility to KOA in Asian but not Caucasian population. There was insufficient evidence to support an association between rs3740199, rs1044122, rs1278279, and KOA. Further case-control studies with large sample size should be performed to confirm our conclusion. Despite the existence of limitation, this study provided an important evidence for the identification of the association between ADAM12 SNPs and KOA.In summary, the results of our current study showed that the polymorphism rs1871054 within ADAM12 was significantly associated with increased risk of KOA and the association may be population dependent, currently only observed in Asian population. In either Asian population or Caucasian population, no statistically significant association between rs3740199, rs1044122, rs1278279, and KOA risk was found. Large-scale studies in different populations are encouraged.


Several population-based studies have been conducted to determine whether maternal exposures are involved in the pathophysiology of autism spectrum disorder (ASD). We review these studies and describe the factors not associated with increased risk for ASD development.We identified studies describing associations between maternal exposures and ASD development. These studies include the Childhood Autism Risks from Genetics and the Environment, Nurses’ Health Study II, and the Swedish population registry.Factors not associated with ASD development include Type 2 and gestational diabetes, chronic hypertension, fever treated with antipyretic medication, autoimmune disease and short interpregnancy intervals.There is increasing evidence that maternal exposures are involved in the pathophysiology of ASD in the developing fetus. Lay Abstract: Autism spectrum disorder currently affects one in 68 children in the USA, with up to one in 42 boys. Its underlying etiology is largely unknown. Although autism was once considered a childhood disease, efforts for early detection led to the realization that it might originate at a much earlier stage, namely fetal life. Several maternal risk factors have recently been studied to establish associations with autism in the offspring. In this review, we present the maternal risk factors that were not found to have such associations. Autism spectrum disorder (ASD) is defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders DSM-5) as persistent deficits in social communication and social interaction across multiple contexts, as manifested by deficits in social-emotional reciprocity, deficits in nonverbal communicative behaviors used for social interaction, or deficits in developing, maintaining and understanding relationships . The cur as persi. Single gene mutations can significantly increase the risk for developing ASD [FMR1 (fragile X syndrome), MECP2 (Rett syndrome), TSC1/TSC2 (tuberous sclerosis complex) as well as several others [The underlying etiology for ASD is largely unknown; however, there are many theories related to the pathogenesis of the disorder. The etiology is thought to involve genetic, neurobiological as well as environmental factors though the role of each individual factor is still being discovered. It has been previously shown that individual genetic mutations account for a relatively low percentage of the overall number of ASD casesping ASD . These il others ,9. Reporl others  and othel others . This wiet al. [et al. subsequently published an article defending the ‘autism-mercury hypothesis’ [Connors et al.  describeothesis’ . Continuothesis’ . Furtherothesis’ . Childhoothesis’ ,18,19 haThough ASD was once considered a childhood disease, efforts for early detection led to the realization that it might originate at a much earlier stage, namely fetal life . There aWe performed a review of the scientific literature to find any associations observed in fetal life that are linked to ASD development. To identify publications discussing associations between maternal environmental exposures and the development of ASD, a search of Pubmed and EMBASE databases through February 2015 was conducted to identify pertinent articles using the search terms ‘autism’, ‘pregnancy’, ‘ASD’, in all combinations with the terms ‘metabolic conditions’, ‘fever’, ‘autoimmune disorder’, ‘infection’ and ‘obesity’. Much of the data available were obtained through population-based studies. In many cases, data collection in these studies was not tailored only for ASD development. However, currently there are no experimental studies using animal models showing a causal effect between an environmental insult and the development of ASD; thus these population-based studies provide a platform for which to begin researching this important topic.In this review, we would like to detail which associations have been determined through population-based studies to not be associated with the development of ASD.Several large population-based studies have been done to determine the risk of ASD development. These studies have been done in several different population groups including American and European cohorts representing varied demographic backgrounds. According to Szklo, there are three primary advantages to the population-based study design . The firThe Childhood Autism Risks from Genetics and the Environment (CHARGE) study  was doneThe Nurses’ Health Study II (NHS II) is a prospective cohort of 116,608 female nurses aged 25–42 when recruited in 1989, who have been followed by biennial mailed questionnaires to assess the incidence of cancer and other chronic diseases. Completion and return of questionnaires sent by US mail constitutes implied consent. The 2005 questionnaire included an item asking women if they had a child diagnosed with autism, Asperger syndrome or ‘other autism spectrum disorder’. Only women who had given birth at least once before the end of 2003 and returned the 2005 questionnaire when the outcome was assessed were included; this provided a primary study population of 66,445 women. Among those women, 9477 had their first birth in 1989 or later and were included in the prospective subgroup sensitivity analysis, while 11,287 women had only one pregnancy and were included in the uniparous sensitivity analysis.Several studies have been published in Sweden due to nationwide registries available for analysis. The Swedish population register system retains routinely collected health and sociodemographic data on the entire population of Sweden. The registers are cross-linked using a unique national registration number assigned to all Swedish residents at birth (or upon migration to Sweden) . The ascCurrently, these studies present the only data available on these associations. Many factors were evaluated and many associations were discovered; however, follow-up studies will need to be done to ascertain whether true causative roles are present for the associations found.Based on the CHARGE study, the following environmental factors failed to show a significant association with ASD development: Type 2 and gestational diabetes , hyperteBased on the NHS II maternal self-reported history of gestational diabetes failed to show a significant association with ASD development .Based on data published from the Swedish nationwide registry the following environmental factors failed to show a significant association with ASD development: maternal diabetes , maternaMaternal hypertension, gestational diabetes and febrile illness during the first trimester are factors that are not associated with the development of autism spectrum disorder. The role of pre-eclampsia, and eclampsia might still play a role in causing inflammation within the cerebral cortex early in pregnancy, when the blood–brain barrier is still developing. This suggests that a deeper analysis of early fetal growth and maternal–fetal physiology may still unlock some answers as to the etiology of ASD. In 2013, the American College of Obstetricians and Gynecologists published a task force report on hypertension in pregnancy detailing the reconfigured diagnoses of hypertensive disorders of pregnancy along with revisions on management suggestions for patients with these disorders . One of There is also the possibility of a double-hit hypothesis where a genetic risk factor coupled with an environmental insult at a critical time period during fetal growth greatly increases the odds of ASD development. As detailed earlier, many genes have been postulated to be involved with the development of ASD, which can be potentiated by environmental insults. There appears to be at least one crucial time period between the first and second trimester where the associated risk of ASD development appears to be lower after this checkpoint has been reached. Further research needs to be undertaken to determine potential reasons for this heightened sensitivity prior to this checkpoint.The strength of our analysis is the comprehensive literature search done within PubMED to find large studies that have provided exposure odds ratios connecting environmental risk factors to ASD. As this topic is currently largely unexplored there are no available controlled trials using animal models to connect the maternal–fetal physiology to ASD. Potential weaknesses of the studies include that the cohort within the Swedish population registry, while being the largest available to study potential ASD-risk factors, was not originally set up to study ASD and thus reflects post hoc analysis and that the NHS II study has the potential for recall bias due to its questionnaire format.ASD is a diagnosis with lifelong complications. Its prevalence is increasing at an alarming rate: an increase of greater than 100% in the last decade alone . ChildreMany of the associations that have been discussed in this paper appear to have increased odds ratio for the development of ASD however these values have not been shown to be significant by themselves, and the data preclude us to form deeper conclusions. Further research needs to be done in the future to further advance the knowledge about the etiology of this still mysterious disorder. The end goal of this research will be to improve screening of mothers identified as high-risk to have children with ASD for potential early evaluation and intervention that so far has been shown to be the only effective treatment available.In the next decade, we speculate that there will be increasing evidence to the fetal origins of ASD. As further light will be shed into the pathophysiology of this disorder as well as the maternal factors that are implicated in its genesis, fetal intervention as well as change in prenatal care, might lead to a decrease in its incidence. With further understanding of the factors that are truly associated versus not with ASD development, obstetric care can be modified to optimize the effect of these factors especially in key milestone stages of embryonic and fetal development. This can be through maternal dietary modification or management of underlying maternal conditions. In addition, current use of noninvasive prenatal screening using circulating free fetal DNA, and the availability of microarray genetic evaluation via the same technology, can lead to potential early diagnosis of fetuses at genetic risk for ASD. In the near future, we speculate this will be further studied, and at risk fetuses might benefit from modifications of risk factors, undergo gene therapy especially if they carry single genes implicated with ASD, or to start early intervention even earlier.Autism spectrum disorder is a diagnosis with lifelong complications. Its prevalence is increasing at an alarming rate.Currently ASD affects 1 in 68 children in the USA, with up to 1 in 42 boys.ASD etiology is thought to involve genetic, neurobiological as well as environmental factors, however remains largely unknown.A growing literature supports fetal origins of autism pathogenesis.Large population-based studies have looked into various maternal conditions that can be associated with ASD.These studies provide the groundwork to evaluate decisions on appropriate risk factor management for women that are pregnant or are considering pregnancy to lower the risk of ASD development.Lowering anxiety for expecting mothers in knowing that some of these factors have not been proven as causative for autism in the offspring is of invaluable importance.


In the present study, a meta-analysis was performed to analyze the potential association between IL-10 -1082 A>G gene polymorphism and PTB susceptibility.Background: Earlier studies have shown that Methods: A quantitative synthesis was done using PubMed (Medline), EMBASE, and Google Scholar web databases search and meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models.P=0.985; OR = 1.001, 95% CI = 0.863–1.162), homozygous , heterozygous , dominant , and recessive  genetic models. Likewise, no association of IL-10 -1082 A>G polymorphism with PTB risk was observed in Asian and African population for all the genetic models. Interestingly, the dominant model  demonstrated increased risk of PTB in Caucasian population.Results: A total of 22 eligible studies comprising 4956 PTB cases and 6428 healthy controls were included in the analysis. We did not observe any increased or decreased risk of PTB in allelic contrast (G vs. A: IL-10 -1082 A>G gene polymorphism is not significantly associated with overall, Asian and African population. However, this polymorphism is associated with Caucasian population.Conclusions: This meta-analysis concludes that  Mycobacterium tuberculosis (M. tuberculosis or M. tb) is mainly a disease of the lungs mostly of pulmonary type tuberculosis (PTB), which can easily be spread to others by coughing and breathing. Regardless of availability of various effective treatment strategies, which were assumed to eliminate this disease, recent epidemiological figures of the year 2016 shown that TB is once more on the upsurge [Tuberculosis (TB) caused by M. tuberculosis but relatively large number of population remains with no clinical sign of the disease. However, remaining 5–15% of the infected individuals develop active disease later in life [Mycobacteria itself, the host genetic factors may regulate the differences in host susceptibility to TB [Approximately one-third of the world’s population is thought to be affected with  in life . This suty to TB . The ideT helper 1 (Th1) cytokines associated with resistance to infection and Th2 cytokines with progressive disease [Immune response to PTB is regulated by interactions between lymphocytes with antigen-presenting cells and the cytokines secreted by these cell types. Cytokines, their genes and receptors have been implicated in the protective immunity, pathophysiology and in the development of tuberculosis . Manifes disease .IL-10 gene maps on the long arm of chromosome 1 (1q31-1q32) locus and produced by both myeloid cells and T cells. IL-10 signals through a receptor complex consisting of two subunits: IL-10R1, induced on stimulated hematopoietic cells, and the IL-10R2, constitutively expressed on most cells and tissues [ tissues .IL-10, an anti-inflammatory cytokine prevents the protective immune response to pathogens by blocking the production of proinflammatory cytokines, such as TNF-α and Th1-polarizing cytokine IL-12, by directly acting on antigen-presenting cells such as macrophages and dendritic cells [IL-10 may also inhibit phagocytosis and microbial killing by limiting the production of reactive oxygen and nitrogen intermediates in response to IFN-γ and Th1 induced response to TB [IL-10 was shown to be elevated in the lungs and serum of PTB patients [ic cells . IL-10 mse to TB ,9. IL-10in vitro and in vivo studies have demonstrated that the presence of polymorphisms within the coding or noncoding sequences of cytokine genes can alter the efficiency of transcription of these genes and thus the production of cytokines. Interindividual variations in IL-10 production are genetically contributed by polymorphisms within the promoter region. The polymorphism -1082 A>G occurs within a putative Ets (E26 transformation-specific) transcription factor-binding site and may affect the binding of this transcriptional factor and therefore altered levels of this cytokine and may alter Th1/ Th2 balance with major implications in tuberculous infection [The production of cytokines can be modulated both by the stimuli present in the local environment as well as by the genetic factors. Both, nfection ,12.IL-10 -1082 A>G (rs1800896) gene polymorphism on the development of PTB [IL-10 -1082 A>G gene polymorphism on the risk of overall PTB development and its ethnicity-wise distribution.A number of clinical and genetic studies have been performed to consider the effect of t of PTB –34. Resut of PTB –34. IncoIL-10, Interleukin-10 gene (polymorphism OR mutation OR variant) AND tuberculosis susceptibility or TB or Pulmonary tuberculosis or PTB (last updated on June 2016). We examined potentially pertinent genetic association studies by examining their titles and abstracts, and procured the most relevant publication matching with the eligible criteria for a closer examination. Besides the online database search, the references given in the selected research articles were also screened for other potential articles that may have been missed in the primary search.We performed a PubMed, Medline, EMBASE, and Google Scholar web databases search covering all research articles published with a combination of the following key words, i.e. IL-10-1082 A>G gene polymorphism and PTB risk,they must have done case–control studies between clearly described confirmed PTB patients and PTB free controlshave available genotype frequency in the both cases and controlspublished in the English languagedata collection and analysis methodology should be statistically acceptableadditionally, when the case–control study was included in more than one research article using the same subject series, we selected the research study that incorporated the largest number of individuals.In order to minimize heterogeneity and facilitate the proper interpretation of this study, published articles included in the current meta-analysis had to meet all the following criteria, i.e.duplicate or overlapping publicationstudy design based on only PTB casesgenotype frequency not reporteddata of review or abstractThe major reasons for study exclusion were:For each retrieved study, the methodological quality assessment and data extraction were independently abstracted in duplicate by two independent investigators (SAD & RKM) using a standard protocol. Data collection form was used to confirm the accuracy of the collected data by strictly following the inclusion/exclusion criteria as stated above. In case of disagreement between the above mentioned two investigators on any item related with the data collected from the selected studies, the issue was fully debated and deliberated with the investigators to attain a final consensus. Also, in case failure of reaching consensus between the two investigators, an agreement was achieved following an open discussion with the adjudicator (SH). The major characteristics abstracted from the retrieved publications included the name of first author, publication year, the country of origin, source of cases and controls, number of cases and controls, study type, genotype frequencies, and association with pulmonary TB.Methodological quality evaluation of the selected studies was performed independently by two investigators (RKM & SAD) by following the Newcastle–Ottawa Scale (NOS) of quality assessment . The NOSIL-10 -1082 A>G gene polymorphism and risk of developing PTB, pooled ORs and their corresponding 95% CIs were estimated. Heterogeneity assumption was examined by the chi-square-based Q-test [P-value < 0.05. The data from single comparison were combined using a fixed effects model [I2 statistics was employed to quantify interstudy variability and larger values suggested an increasing degree of heterogeneity [t-test .In order to evaluate the association between the d Q-test . Heterogts model , when nots model . Moreoveogeneity . Hardy–Whttp://www.meta-analysis.com/pages/comparisons.html. The Comprehensive Meta-Analysis (CMA) Version 2 software program  was utilized to perform all the statistical analysis involved in this meta-analysis.A comparative assessment of ‘meta-analysis’ based programs was done by using weblink A total of 22 articles were lastly selected after literature search from the PubMed (Medline), EMBASE, and Google Scholar web databases. All retrieved articles were inspected carefully by reading their titles and abstracts, and the full-texts for the potentially relevant publications were further checked for their aptness of inclusion in this meta-analysis , homozygous , heterozygous , dominant , and recessive  genetic models, respectively  in the risk between P=0.466; OR = 0.917, 95% CI = 0.726–1.158), homozygous model , heterozygous model , dominant model , and recessive model   .P=0.165; OR = 1.300, 95% CI = 0.898–1.883), homozygous model , heterozygous model , dominant model , and recessive model  genetic models . Whereas, other genetic models, i.e. allele , homozygous model , heterozygous model , and recessive model  did not show any increased or decreased risk of PTB with IL-10 -1082 A>G gene polymorphism (In Caucasian population four studies were included. Publication bias and heterogeneity were not significant, hence fixed effect models were applied for all the genetic models . We potemorphism .IL-10 is also thought to play an important regulatory role in many bacterial infections [M. tuberculosis involves the identification and uptake of the bacterium by macrophages and dendritic cells [Although various mechanisms have been described for the development of a protective immune response that restricts and controls the infection and thus prevents the progression of the active disease, the reasons underlying active disease progression remain poorly understood . Candidafections ,44. Immuic cells .IL-10 is an essential pleiotropic cytokine which takes part in immunoregulatory activities. Lately, IL-10 gene has been widely studied and some studies suggested that the IL-10 -1082 A>G polymorphism is associated with PTB susceptibility, but the results are inconsistent. The results of studies generated could be having insufficient statistical power of individual studies with small sample sizes or variations that existed in different population. Therefore, we conducted this meta-analysis to provide more accurate statistical evidence of association between IL-10 -1082 A>G polymorphism and PTB susceptibility. Pooled ORs generated from large sample size and sufficient statistical power from various studies have the advantage of reducing random errors [As we know that PTB is one of the most common infectious diseases with a high morbidity and mortality . A well-m errors .In the present study, we have included 22 studies with all the preset eligible criteria of sample size, genotype, inclusion criteria of PTB patients, and healthy controls. Most of the included studies scored five or more stars in NOS quality score assessment and suggested good to moderate quality by clearly stating about the sample size, genotype, inclusion criteria of PTB patients, and healthy controls.IL-10 -1082 A>G polymorphism and PTB susceptibility under any genetic models in overall analysis.Overall, we found that there was no association between IL-10 -1082 A allele leads to increased resistance to PTB. Studies carried out on mice observed that overexpression of IL-10 may not be important for susceptibility to initial infection with M. tb but may play a role in reactivation of the latent disease [These observations suggested that the  disease . Other s disease ,49.IL-10 -1082 A>G polymorphism has no role of increasing or decreasing PTB susceptibility in Asian and African populations. Interestingly, significant association was found with dominant model. This result implied that among different ethnicities, the same gene polymorphism may act differently in PTB susceptibility. Tuberculosis report clarified racial differences of susceptibility to TB [During the subgroup analysis, we found that ty to TB . Thus, tIL-10 -1082 A>G genetic polymorphism cannot be solely responsible for the predisposition of PTB.However, the susceptibility toward PTB is polygenic and multiple candidate genes are likely to be involved in determining resistance or susceptibility to TB . Due to In the present study, significant heterogeneity was found between the selected studies in the test of heterogeneity. This discordance may be related to the ethnic origin of the patients as ethnicity-specific genetic variations may influence the host immunity to PTB. Nevertheless, some limitations also need to be addressed. First, we only included studies published in the English language, abstracted and indexed by the selected electronic databases were included for data analysis; it is possible that some pertinent studies published in other languages and indexed in other electronic databases may have missed. Second, the abstracted data were not stratified by other factors, e.g. HIV status or severity of the TB infection, and our results were based on unadjusted parameters. Third, we did not test for gene–environment interactions because of inadequate data available in the published reports. Despite above limitations, there are some advantages of the present study. First, the present meta-analysis was comprised with more number of studies which increased the statistical power of the study and ultimately reached at robust conclusion. Second, no publication bias was observed and further sensitivity analysis also supported our results more reliably.Also, all the included studies were of good to modest quality fulfilling the preset needful criteria as tested by NOS quality score evaluation scale.IL-10 -1082 A>G gene polymorphism is not associated with PTB risk in overall, Asian and African population. Our result provided evidence that G allele carrier is associated with PTB in Caucasian population. In the near future, because of significant public health impact of PTB, larger studies are warranted to identify the host genes with their functional allele controlling the response to mycobacterial infections. This will help in the identification of the host genetic factors for the susceptibility to PTB, and would greatly help in the global control of this infectious disease.In conclusion, this meta-analysis demonstrated that


Observational studies assessing the association of dietary fat and risk of ovarian cancer yield discrepant results. Pertinent prospective cohort studies were identified by a PubMed search from inception to December 2015. Sixteen independent case-control and nine cohort studies on dietary fat intake were included, with approximately 900,000 subjects in total. Relative risks (RRs) with 95% confidence intervals were pooled using a random effects model. Heterogeneity, sensitivity analysis and publication bias were assessed; subgroup analysis and analysis stratified by EOC histology were conducted. The reported studies showed a significant increase of ovarian cancer risk with high consumption of total-, saturated-, and trans-fats, while serous ovarian cancer was more susceptible to dietary fat consumption than other pathological subtypes. No evidence of positive association between dietary fat intake and ovarian cancer risk was provided by cohort studies. Menopausal status, hormone replacement therapy, body mass index (BMI), and pregnancy times, modified the objective associations. In conclusion, the meta-analysis findings indicate that high consumption of total, saturated and trans-fats increase ovarian cancer risk, and different histological subtypes have different susceptibility to dietary fat. Ovarian cancer is considered the sixth most commonly diagnosed cancer among women and the second cause of gynecologic cancer mortality worldwide , 2. The Dietary fat, as one of the most controversial dietary factors in nutritional epidemiology, has been reported with positive correlations with breast  and gastWe found 1421 publications from the electronic and manual literature searches. Thirty-three potentially relevant publications –31 32–4–432–47  appearedFinally, Twenty-five publications –31 32–4–432–40, P = 0.017) for case-control and 1.10  for cohort studies, with an overall RR of 1.19  for all studies. These results suggested a positive association between total fat intake and ovarian cancer risk.  for case-control, and 1.09  for cohort studies; the overall RR was 1.21  for all studies. Taken together, these results suggested no association between animal fat intake and ovarian cancer risk.  for case-control, and 0.93  for cohort studies, with an overall RR of 0.95 . These results suggested no association between plant fat intake and ovarian cancer risk.  for case-control, and 1.06  for cohort studies; the overall RR was 1.09 . After exclusion of 1 study [P = 0.026), 1.06 , 1.12 , without heterogeneity  between studies. These results suggested a positive association between saturated fat intake and ovarian cancer risk.  for case-control, and 1.04  for cohort studies; the overall RR was 0.98  for all studies. These results suggested no association between total fat intake and ovarian cancer risk.  for case-control, and 1.06  for cohort studies, with an overall RR of 0.97  for all studies. These findings suggested no association between polyunsaturated fat intake and ovarian cancer risk.  for cohort studies, with an overall RR of 1.05  for all studies. These results suggested no association between dairy fat intake and ovarian cancer risk.  for case-control, and 1.24  for cohort studies; the overall RR was 1.25  for all studies. These results suggested a significant positive association between trans-fat intake and ovarian cancer risk. , suggesting a significant positive association between animal fat consumption and mucinous ovarian cancer risk.  and dairy fat  intake could increase ovarian cancer risk in European populations; a positive trend was present among American populations, while an inverse trend was found in other populations (including Asians and South Americans). The conclusions of case-control and cohort studies were basically consistent; however, cohort studies were more inclined to a positive association between dietary fat intake and ovarian cancer risk, though no statistical significance was obtained. The summary results were modified by menopausal status, hormone replacement therapy, BMI, and pregnancy times. Table .Sensitivity analysis showed that the results obtained for the association between saturated fat intake and ovarian cancer risk were significantly influenced by one study , which dP > 0.05).We found no evidence of publication bias with regard to dietary fat consumption and ovarian cancer risk by means of visual inspection of funnel plots and formal statistical tests, including Begg rank correlation test and Egger linear regression test . Stomach cancer was considered to be linked more with eastern lifestyle. The included two meta-analyses , 8 indicThe results of this meta-analysis including case-control and cohort studies indicated that consumption of total dietary fat and trans fat increased the risk of ovarian cancer. These findings were consistent with the results in specific epidemical studies in NIH-AARP cohort study  and an evia mitogenic effects on ERα- positive [Subgroup analysis based on the characteristics of included studies suggested that menopausal status, hormone replacement therapy, BMI, and pregnancy times can modify the association between dietary fat intake and ovarian cancer risk. These factors are related to exposure to estrogens , 65. A rpositive , 71 or npositive  tumor cepositive . What's positive  and leadpositive , 75.An important highlight of our meta-analysis is that we analyzed the association between dietary fat intake and the risk of ovarian cancer subtypes. We found that serous ovarian cancer incidence was more susceptible to dietary fat intake. However, these results should be interpreted with caution. The insufficient number of included cases and potential misclassification of pathological subtypes may contribute to the statistical difference observed.Several limitations of this meta-analysis should be considered. First, there was substantial heterogeneity across studies assessing the associations of dietary fat intake with ovarian cancer risk. Considering the varieties of the characteristics of included populations, and study designs and types, the existence of substantial heterogeneity was reasonable, and we conducted subgroup analysis to reduce its effect on the results. Second, misclassification bias, which stemmed mainly from the misclassification of dietary assessments and pathological subtypes of ovarian cancer, should be paid enough attention to. Misclassification of dietary assessments may result from the differences across nutrient databases or designed questionnaires. Diagnosis, pathology review, and classification methods could cause misclassification bias of pathological subtypes of ovarian cancer. Third, we couldn't rule out the effects of confounding factors and various statistical biases on our results. Furthermore, controls and confounding factor adjustment methods across individual studies were not consistent. With more and more basic and clinical researches in recent years, and the increasing understanding of the relationship between diet and health, the confounding factors controlled have markedly increased in number, and bias was inevitable. Forth, although no publication bias was found, its possible effect cannot be totally excluded.In conclusion, the present meta-analysis of case-control and cohort studies indicate that increased consumption of total fat, saturated fat and trans-fat may be associated with an increased risk of ovarian cancer. Among the dietary fats, saturated fats can significantly increase serous and endometroid ovarian cancer, with the risk of serous ovarian cancer more susceptible to dietary fat intake. In addition, subgroup analysis data suggested that menopausal status, hormone replacement therapy, BMI, and pregnancy times may serve as potential effect modifiers. Future studies should focus more on specific pathological subtypes of ovarian cancer as well as the influence of molecular mechanisms and genetic factors on the association of dietary fat and ovarian cancer.We obtained the literature published in any language to December 2015 by fully searching the PubMed database. The search terms used were “diet”, “dietary fat” in combination with “ovarian cancer,” “ovarian neoplasm” or “ovarian carcinoma”, without restrictions. In addition, we reviewed the reference lists of retrieved studies and recent reviews to supplement electronic database searches.Study selection included initial screening of titles or abstracts, and a second one for full texts. Studies were eligible for inclusion if they met the following criteria: 1) observational studies which enrolled patients with proven epithelial ovarian cancers excluding tumors of “borderline malignant potential” histopathology, 2) patients enrolled were adults (≥18 yr of age), 3) studies containing available data showing association(s) between intake of dietary fat  and ovarian cancer, and 4) odds ratio or relative risk (RR) with 95% confidence interval (CI) for each variable or availability of raw data to calculate these parameters.versus lowest category of dietary fat intake with the corresponding 95% CI; statistical adjustment for the main confounding factors of interest.All data were extracted with a data-collection form. Information was recorded as follows: last name of the first author, publication year, study population, period, country, sample size; risk estimate from multivariable model for the highest Data extraction and study selection were performed by 3 authors  independently. Any disagreements were resolved by discussion.P < 0.10) and I2 statistic, a quantitative measure of inconsistency across studies [P > 0.05). The Stata version 12.0 software (StataCorp) was used for statistical analyses.The association between dietary fat consumption and the risk of ovarian cancer was our main analytical object. Dietary fats in this meta-analysis were defined as total fat, animal fat, plant fat, dairy fat, saturated fat, monounsaturated fat, polyunsaturated fat and trans-fat. Relative risk (RR) was used as the common measure of association in this meta-analysis, and the random-effects model was selected to calculate summary RRs and 95% CIs associated with dietary fats. Q statistic (significance level at  studies , were ap studies , and Beg studies  (all P >


Approximately half of recurrent miscarriages have unexplained etiology. Recent evidences suggest that cytokines are important determinants in pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect cytokine production and/or functionality, could play a role in the disorder. Thus, we aimed to investigate the association of selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese.TNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms were genotyped on 775 women with idiopathic recurrent miscarriage and 805 healthy parous control women. Logistic regression analysis was performed to determine the odds ratios (ORs) of the association between the polymorphisms and recurrent miscarriage risk.IL1B -511 T > C and IL6 -634C > G polymorphisms showed statistically significant associations with recurrent miscarriage risk. For the former, a significantly increased risk of recurrent miscarriage was observed for the mutant (CC) genotype . However, for the IL6 -634C > G polymorphism, a decreased recurrent miscarriage risk was observed for the heterozygous (CG) genotype  and the mutant (GG) genotype .Among the eight polymorphisms studied, only the IL1B -511 T > C polymorphism may serve as important risk factor for recurrent miscarriage while the IL6 -634C > G polymorphism may protect against the risk of recurrent miscarriage.The  Recurrent miscarriage refers to the consecutive loss of pregnancy before the 20th gestational week for three or more times . This evRecently, the contributions of immunogenetic factors to the etiopathology of recurrent miscarriages have been suggested . During TNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T. All the cytokines studied are Th1 cytokines, except IL10, which shows dual (inhibitory and stimulatory) immunologic functions and thus could not be classified as either Th1 or Th2 [The expression of cytokines, as well as the immune response elicited, could be influenced by polymorphisms in cytokine genes. Thus, cytokine gene polymorphisms could potentially influence the risk of recurrent miscarriage. In this study, we investigated the association of eight selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese women. The cytokine gene polymorphisms selected were 1 or Th2 . HoweverThe study was approved by the Institutional Review Board of People’s Hospital of Yuyao City, Zhejiang Province . The study was conducted in accordance to the Declaration of Helsinki. Written informed consent was obtained from all participants before being included in the study.All young women (age ≤ 40 years) with recurrent miscarriages were identified from the obstetrical department of the People’s Hospital of Yuyao City, Zhejiang Province between December 2011 and January 2017. All women were at active (non-menopause) phase of menstruation. Recurrent miscarriages were defined as having a minimum of three clinically detectable spontaneous abortions before the 20th gestational week. Women with a history of diabetes or hypertension, drug or alcohol abuse, and smoking were excluded. Of the 2038 eligible women, 1742 agreed to participate in the study. A number of tests were performed to identify the causes of recurrent miscarriage among all these women, including hysterosalpingography, ultrasound, parental karyotypic analysis, examination of luteal phase defects, measurements of anti-phospholipid antibodies and lupus anticoagulants, examination of TORCH infections, tests of autoimmune disorders and erythroblastosis fetalis (Rh incompatibility) and other in-house examinations. In some but not all women, additional tests such as saline-infusion sonohysterography, hysteroscopy or endocrine tests were also performed. After exclusion of the participants with known causes of recurrent miscarriages, 775 patients were classified as being idiopathic and were recruited into the study. Meanwhile, 805 healthy parous women were recruited as controls. Controls were women who had at least 3 successful live births, with no history of miscarriages or preterm birth, and aged-matched to the cases. At recruitment, the interval from the last event (miscarriage or delivery) of the women ranged from 3 to 11 months (mean: 7.36 months). All participants were Han Chinese in ethnicity. A total of 5 ml blood specimen was collected from each participant for genetic analysis. Only 200 μl of the blood was eventually used, and the remaining was stored in our institution bio-repository for future use.Genotyping was performed on genomic DNA derived from the 200 μl blood specimens of the participants. Genomic DNA was isolated with the ethanol precipitation method using TIANamp Blood DNA kit . Briefly, blood sample from each participant was sequentially mixed with 20 μl Proteinase K and 200 μl Buffer GB, and incubated at 56 °C for 10 min. After a homogenous mixture was formed, 200 μl absolute ethanol was added to precipitate the DNA. The mixture was transferred to a Spin Column CB3 and centrifuged at full speed for 30 s. The spin column was then washed sequentially with 500 μl Buffer GD and 600 μl Buffer PW and centrifuged at full speed for 30 s and 2 min respectively. After the washing step, the DNA was eluted at 100 μl Buffer TB and used for genotyping of the polymorphisms.IFNG 874A > T polymorphism, which was genotyped by allele-specific PCR. All PCR reactions were performed with Tiangen Fast HiFidelity PCR Kit  on a Bioer Life Express thermocycler . The PCR primers used for genotyping of the polymorphisms are shown in Table All polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assays, except the P < 0.05.Frequencies of the polymorphic genotypes were calculated by direct counting. Differences in the genotype frequencies between cases and controls were evaluated with chi-squared analysis. Each polymorphism was evaluated for possible deviation from the Hardy-Weinberg equilibrium by using a goodness-of-fit test. Logistic regression analysis was done to calculate the odds ratios (ORs) of the risk of recurrent miscarriage contributed by the polymorphisms. All statistical tests were two-sided and were performed with SPSS software version 19. All comparisons were considered to be statistically significant at IL6 -634C > G polymorphism (P < 0.001), with the wild type (CC) genotype observed to be overrepresented in the cases and the heterozygous (CG) and mutant (GG) genotypes observed to be overrepresented in the controls. The CC, CG and GG genotypes were seen in 554 (71.5%), 197 (25.4%) and 24 (3.1%) of the cases, and 478 (59.4%), 277 (34.4%) and 50 (6.2%) of the controls, respectively.The eight polymorphisms were successfully genotyped in all 775 cases and 805 controls. All results obtained from initial genotyping methods  agreed with the independent confirmatory sequencing reactions. The frequencies of the polymorphic genotypes among the study participants are shown in Table IL1B -511 T > C polymorphism did not differ significantly between the cases and controls, the P value was at the borderline of statistical significance (P = 0.079). Contrary to the IL6 -634C > G polymorphism, the wild type (TT) genotype of the IL1B -511 T > C polymorphism was found at a higher frequency in the controls, while the heterozygous (TC) and mutant (CC) genotypes were observed more frequently in the cases. The TT, TC and CC genotypes were respectively present in 213 (27.5%), 384 (49.5%) and 178 (23.0%) of the cases, and 257 (31.9%), 392 (48.7%) and 156 (19.4%) of the controls.It is also noteworthy to mention that although the genotype distribution of the P values of 0.308 (TNF -238G > A polymorphism), 0.307 (TNF -308G > A polymorphism), 0.777 (IL1B 3954C > T polymorphism), 0.135 (IL6 -174G > C polymorphism), 0.186 (IL10 -1082A > G polymorphism) and 0.589 (IFNG 874A > T polymorphism), respectively.A clear lack of statistical significance was observed for the genotype distribution of the remaining polymorphisms, with The genotype distribution of all the eight polymorphisms conformed to the Hardy-Weinberg equilibrium in both cases and controls Table .Table 3LIL1B -511 T > C polymorphism (P = 0.026), as well as the heterozygous (CG) and mutant (GG) genotypes of the IL6 -634C > G polymorphism (P < 0.001 and P = 0.001 respectively). The mutant (CC) genotype of the IL1B -511 T > C polymorphism was associated with an increased risk of recurrent miscarriage, with an OR of 1.377 : 1.039–1.824). On the contrary, a decreased risk of recurrent miscarriage was noted for the heterozygous (CG) and mutant (GG) genotypes of the IL6 -634C > G polymorphism, which showed an OR of 0.614 (95% CI: 0.493–0.765) and 0.414 (95% CI: 0.251–0.684) respectively.Next, logistic regression analysis was performed to find out the odds ratio (OR) of each polymorphic genotype in contributing to the risk of recurrent miscarriage. The results were presented in Table TNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms.Fine regulation of cytokine levels is essential for a successful pregnancy. Improper balance in the levels of Th1 and Th2 cytokines has been known to contribute to recurrent miscarriage , 7. CytoIL1B -511 T > C polymorphism and IL6 -634C > G polymorphism showed a statistically significant association with recurrent miscarriage risk. The IL1B -511 T > C polymorphism was found to be associated with an increased risk, with the mutant (CC) genotype having an OR of 1.377 (95% CI: 1.039–1.824). This finding was similar to a previous study in Korea [IL1B -511 T > C polymorphism was not associated with recurrent miscarriage risk, which was in contrast with our findings. However, it should be noted that great discrepancies exist in different subpopulations of China, and these discrepancies may affect the influence of the polymorphism on recurrent miscarriage risk. We studied the association between the polymorphism and recurrent miscarriage risk among residents of Zhejiang Province, while the previous work investigated the association in Jiangsu Province. This could explain the inconsistency in the finding obtained. Moreover, our study included a much larger number of participants compared to this previous work (1580 participants in the present work vs. 318 participants in the previous work), which provide a greater accuracy for our findings.Among these polymorphisms, only in Korea , which sin Korea . Apart fin Korea . The autIL6 -634C > G polymorphism was associated with a decreased risk of recurrent miscarriage, with the heterozygous (CG) genotype showed an OR of 0.614 (95% CI: 0.493–0.765) and the mutant (GG) genotype showed an OR of 0.414 (95% CI: 0.251–0.684). There were also two previous studies which investigated the association of this polymorphism with recurrent miscarriage risk, including one study from China [In this study, we also showed that the om China  and one om China . ConsistTNF -238G > A and -308G > A polymorphisms with risk of recurrent miscarriage. These two polymorphisms have been frequently investigated in the context of recurrent miscarriage, but the results obtained have been inconsistent [TNF -238G > A polymorphism was found to be significantly more common in the cases. This means that the A allele was significantly associated with a decreased risk of recurrent miscarriage. Consistent with this previous work, our study showed that carriers of the A allele had a lower risk of recurrent miscarriage, although our observation did not reach statistical significance. Several other studies concurred with our findings [TNF -308G > A polymorphism with recurrent miscarriage risk in the Chinese population. This is consistent with a few previous reports [We did not find any significant association of nsistent , 15, 18.findings , 12, whifindings , 18. The reports , 14, 18,IL1B 3954C > T, IL6 -174G > C, IL10 -1082A > G and IFNG 874A > T polymorphisms with the risk of recurrent miscarriage. There was only one previous study which investigated the former (IL1B 3954C > T polymorphism) in recurrent miscarriage [IL10 -1082A > G polymorphism had also been investigated in the South Korean population [We also did not find an association of carriage , and thepulation , and no Our study had the strength in the statistical power. We included a total of 1580 participants (775 cases and 805 controls), which is the largest set of participants ever investigated for these eight polymorphisms. However, one limitation is that we did not adjust our findings by other potential confounding factors. This was due to the local legislation scenario, which disallowed us to access certain data of the patients. However, to minimize the influence of the confounding factors, we matched the participants carefully by age, and did not include participants with diabetes or hypertension, drug or alcohol abuse, and smoking habit. Despite this, future studies are needed to confirm our findings.IL1B -511 T > C polymorphism was significantly associated with an increased risk of recurrent miscarriage, while the IL6 -634C > G polymorphism was significantly associated with a decreased risk of recurrent miscarriage. These polymorphisms may potentially serve as important biomarkers for predicting recurrent miscarriage risk among Chinese. Future studies should embark on this research direction.We showed that the


COMT, OMIM: 116790) was studied. Here 100 BPD patients, 100SCZ patients, and 100 healthy controls were included in the study. The samples were matched in terms of gender and ethnicity. Statistical analysis showed that there was a significant association this polymorphism and risk of SCZ. The AG  and GG genotypes  increased the risk of SCZ compared with the GG genotypes. The AG  and AA genotypes  significantly associated with the risk of BPD. The risk of SCZ  and BPD  significantly increased as a function of numbers of the A allele. The present study revealed that this polymorphism associated with risks of SCZ, and BPD.Linkage studies and epidemiological findings indicate that some possible genes in schizophrenia (SCZ) and bipolar mood disorder (BPD) are common. Numerous evidences for linkage of two diseases on chromosome 22 have been found. These findings suggest that one or more genes in the 22q11.21 region may be involved in the development of both disorders. In the present case-control study, association between the mentioned disorders and a genetic polymorphism (rs165599) of catechol O- methyltransferase ( Psychiatric disorders are the third largest health problem in developed countries. Schizophrenia (SCZ) and bipolar mood disorders (BPD) are samples of chronic disorders that are costly and heavy burdens for society and family . Both SCLinkage studies and epidemiological findings led to the suggestion that some genes associated with BPD and SCZ are common . EvidencCOMT, G72 and DISC1, may also be associated with BPD [COMT, OMIM: 116790) gene (located on human chromosome 22q11) has been studied in several mental disorders associated with SCZ [COMT may be involved in their mental disorders. The COMT protein affects the dopamine destruction, which has been proved as a potent neurotransmitter in many studies [COMT with risk of SCZ and BPD.Genetic studies have revealed that first- or second-degree relatives of individuals with SCZ or BPD are at high risk for these two disorders. Recent studies emphasize that increased risk of mental illness in relatives of probands with SCZ, is not limited to SCZ . In the with BPD , 11. Catwith SCZ . In addiwith SCZ . Accordi studies . The rs1 studies , 15. COM studies . The maiClinical samples collection: Based on DSM-IV-TR standard, 100 blood samples of patients with SCZ (67 men and 33 women) and 100 patients having BPD (47 men and 53 women) on their admissions in Golestan hospital  were collected. The patients were evaluated by at least two psychiatrists during their admission. All the patients were treated with anti-psychotic and/or mood stabilizers drug during evaluation. The control group consisted of 127 non-relative  individuals whom were screened in two steps. Firstly, they were interviewed using a questionnaire which showed that the individual or his/her first and second degree relatives are not at least one of the following: history of referral to a psychiatrist or psychologist, history of consuming psychiatric drugs, psychiatric hospitalization history, history of suicide attempts, and history of substance abuse or dependency.Secondly, the screening was completed by GHQ . These criteria resulting in only the healthy subjects were included in the study. Healthy control, SCZ patients and BPD patients subsequently had mean±SD age 37.6±9.6, 36.9±10.2 and 34.4±11.2.DNA extraction and genotyping analysis: Genomic DNA was prepared from blood samples through use of the Diatom DNA extraction kit . The concentration of the genomic DNA was determined in an Uvisco UV/V-1200 Symantec (Switzerland) spectrophotometer. For the amplification of the DNA following primers were used: SNP rs165599-F: 5'-CAC AGT GGT GCA GAG GTC AG-3' and R:5'-TCA TCA CCA TCG AGA TCA ACC-3'. 10 µl of PCR product was digested with 3 µl MspI , in a total reaction volume of 15 ml containing 2 µl of commercial buffer and were subjected to the following cycling protocol: 95°C for 10 min; then 94°C for 30 sec, 60°C for 30 sec, and 72°C for 30 sec, for 35 cycles; followed by 72°C for 10 min. Fragments were separated on 3%agarose gel stained with safe stain .Statistical analysis: The results were analyzed using the statistical software SPSS16, logistic regression. The results evaluated at significance level P<0.05.COMT in the BPD, SZC and control groups. Control subjects were at Hardy-Weinberg equilibrium . Statistical analysis showed that there was a significant association this polymorphism and risk of SCZ. The AG  and GG genotypes  increased the risk of SCZ compared with the GG genotypes. Comparison between BPD and control subjects revealed same associations. It means that the AG  and AA genotypes  significantly associated with the risk of BPD. The risk of SCZ  and BPD  significantly increased as a function of numbers of the A allele.COMT gene, affects the enzyme activity and physiology of human cortex. High activity allele, Val, increases SCZ risk through effects on early information processing by dopamine. The polymorphism of Val/Met has been studied by many researchers [It is known that common functional polymorphism Val/Met earchers , 20. Shiearchers  observedearchers , showed earchers  and collCOMT gene, especially one SNP that is located in the 3' untranslated region close to exon 1 of MB-COMT isoforms; rs165599 have reported that expression of COMT is associated with risk of SCZ [As a result other SNPs in the k of SCZ , 24. Shik of SCZ . The assk of SCZ . Howeverk of SCZ .COMT gene, SCZ and BPD, there are some study with different results. These conflicting results may be interpreted using following reasons:Despite many reported association between - One of the most important causes is population differences.- Another possible cause is related to how subjects are selected. Psychiatric interview or various test are methods of detection of mental disorder.COMT gene with SCZ and BPD have been done. The rs165599 polymorphism of COMT has not yet been widely studied. The present study revealed that this polymorphism associated with risks of SCZ, and BPD.In the present study the GHQ test has been applied to diagnose healthy individuals, provided that they own no first or second degree relatives who have a history of mental illness no drug addiction, and no inpatient psychiatric drugs, then association studies on polymorphism of


Previous epidemiological studies have suggested that genetic factors are more likely to influence the development of premature coronary artery disease (CAD) than disease in older patients. Several studies have evaluated the association between the G894T polymorphism located in an exon of endothelial nitric oxide synthase (eNOS) and the risk of premature CAD. However, the findings were inconsistent. Thus, we performed a meta-analysis to clarify the association; we conducted both overall and subgroup analyses. Odds ratios and 95% confidence interval were calculated to evaluate the association between the G894T polymorphism and the risk of premature CAD. Overall analysis revealed a significant association. Subgroup analysis in terms of ethnicity revealed a significant association, in all models evaluated, between the G894T polymorphism and susceptibility to premature CAD in mixed population. In contrast, no such association was evident in Caucasians and Asians. On further subgroup analysis based on the premature CAD subtypes, we found that the G894T polymorphism was correlated with premature myocardial infarction (MI) but not with premature CAD without MI. In conclusion, we confirmed that the eNOS G894T polymorphism is a risk factor for premature CAD, particularly in those suffering premature MI. Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide . GeneticPrevious studies found that endothelial dysfunction plays a critical role in atherosclerosis progression –8. EndotNO production levels are influenced by several polymorphisms in the eNOS gene located on chromosome 7q35–36; the gene contains 26 exons with a total length of 21 kb, and the encoded protein is responsible for intracellular NO production . Over thA variant of the eNOS gene within exon 7, a G→T transversion at nucleotide position 894 of the cDNA, changes Glu298 (GAG) to Asp (GAT) . SeveralP > 0.05). The characteristics of the included studies are summarized in Table A total of 345 relevant studies were identified by the initial search. After full-text review, 335 studies that did not meet the inclusion criteria, contained inadequate data, or were duplicates were excluded. Finally, 10 studies were included –24. The P values for heterogeneity. Overall, we found a significant association between the G894T polymorphism and premature CAD in the allelic  and recessive  models, but not in the dominant model .Figure P = 0.005), 1.64 , and 2.25 , respectively , 1.24 , and 1.55 , respectively. The ORs for the Asian subgroup were 0.83 , 0.85 , and 0.55 , respectively , Asian (two studies recruited 245 cases and 196 controls) and mixed population (three studies recruited 411 cases and 403 controls). We found a significant association between the G894T polymorphism and the risk of premature CAD among mixed population when the allelic, dominant, and recessive models were employed. The ORs for the mixed population subgroup were 1.62 , 1.36 , and 1.65 , respectively , 1.24 , and 1.71 , respectively  or Egger's regression test . The funnel plots were not asymmetric , genetic factors also play important roles in pathogenesis and disease development , 25. ThoTo the best of our knowledge, our present meta-analysis of 10 studies and 3,990 participants is the first to assess the association between the G894T (Glu298Asp) eNOS polymorphism and the risk of premature CAD. Our overall analysis revealed a significant association between the polymorphism and the risk of premature CAD in all three genetic models evaluated, indicating that the polymorphism may play an important role in the development of premature CAD.The influence of genetic polymorphisms can be complicated and may differ among various races and geographical regions. Thus, we performed stratification analyses by patient ethnicity. All models revealed a significant association between the G894T polymorphism and premature CAD in mixed populations, but not in Caucasians and Asians. However, only two of the studies focused on Asian populations in this meta-analysis. Further studies are essential to determine whether the observed geographical variability is attributable to differences in genetic backgrounds. Upon further subgroup analyses according to CAD subtype, the G894T polymorphism was correlated with the development of premature MI, but not premature CAD. A possible explanation is that different genetic variants influence the development of coronary atherosclerosis and MI, consistent with the observations of prior studies –35. In aSome limitations of our work should be addressed. First, although we collected all eligible studies, the sample sizes were small, particularly in the subgroup analyses, increasing the risk of false-positives or -negatives. Studies with larger sample sizes are required. Second, progression of premature CAD is multifactorial. Given the limited data, we did not analyze our findings in terms of disease, age, or sex. Certain environmental and lifestyle factors may influence the observed associations. The potential roles played by smoking, hypertension, diabetes mellitus, and obesity must be evaluated. Third, although neither the funnel plot nor Egger's test revealed any publication bias, such bias remains possible.In conclusion, we found that the G894T polymorphism was associated with a risk of premature CAD, particularly in those experiencing premature MI. Thus, testing for the eNOS G894T polymorphism may be useful for clinical assessment and prediction of premature CAD.Two independent reviewers searched Pubmed, Embase, the Chinese Biomedical Literature Database, and the Cochrane library database (up to December 2016) using the following terms:  AND (‘premature’ OR ‘young’ OR ‘early onset’) AND . We perused the reference lists of retrieved articles to identify further potentially relevant studies. Any disagreement was resolved by discussion among the team. We retrieved only texts in English and Chinese. If studies contained overlapping data, only the study with the largest group of subjects, or the most recent study, was included.The inclusion criteria were studies (1) that assessed the association between the G894T (Glu298Asp) polymorphism and the risk of premature CAD/MI, (2) that were either a case-control or a cohort study, (3) in which all patients had been diagnosed with premature CAD/MI, and the healthy controls did not have CAD, (4) in which the CAD diagnosis was based on coronary angiography and the MI diagnosis on electrocardiography and clinical and laboratory data, and (4) in which the genotype distributions of the controls were in Hardy–Weinberg equilibrium (HWE).We excluded reviews, case reports, letters, editorials, conference abstracts, and duplicate publications of data from the same study.Data were extracted independently by two authors; any disagreement was resolved by discussion among the review team. We extracted the name of the first author, publication year, patient ethnicity, study design, definition of the cases, source of the controls, mean age, age range, male percentage, numbers of cases and controls, genotype distributions of the cases and controls, and the genotyping method used. Authors were contacted with requests for original data when such data were absent from the reports.The quality of eligible studies was assessed by using the Newcastle-Ottawa scale (NOS). NOS quality scores ranged between 0 and 9 stars. Studies with a score ≥ 7 were considered high quality, while studies with a score ≤ 5 were deemed low quality.Q test and I2 statistics. A P value < 0.05 or an I2 value > 50% indicated that heterogeneity was in play among studies; the random-effects Mantel–Haenszel model was used to compare the data of such studies. Otherwise, the fixed-effects Mantel–Haenszel model was employed. Subgroup analysis was performed by ethnicity and CAD subtype. Publication bias was assessed by drawing a funnel plot and using Egger's test. During the sensitivity analysis, we omitted individual studies to evaluate the reliability of our results. All data were analyzed using STATA 12.0 software for Windows. A P value < 0.05 was considered to reflect statistical significance.The association between the eNOS G894T polymorphism and the risk of premature CAD was assessed by calculating odds ratios (ORs) with 95% confidence intervals (CIs). We performed an overall comparison as well as a stratification analysis based on patient ethnicity. Each OR and 95% CI were calculated by reference to an allelic model (T vs. G), a dominant model ([GT + TT] vs. GG), and a recessive model (TT vs. [GG + GT]). The chi-squared test was used to determine whether the control genotype distributions were in HWE. Heterogeneity among studies was evaluated by calculation of


The role of progesterone receptor (PGR) gene polymorphisms in breast cancer is still controversial. Here, we performed a meta-analysis to determine whether the Alu insertion is associated with an increased risk of breast cancer and, further, whether the Alu insertion contributes to the development of breast cancer.Using database searches, we selected 10 controlled case studies that met a rigorous set of inclusion criteria; these studies included 2106 cases and 1660 controls. We generated odds ratios and 95% confidence intervals in order to determine the strength of the relationship between the Alu insertion and breast cancer incidence. We also performed additional subgroup analyses and sensitivity analyses to further clarify the relationship.p = 0.943). When a subgroup analysis was performed according to ethnicity, we found that the Alu insertion was associated with breast cancer incidence in Indians and Indo-European mixed racial groups, but the association disappeared for patients of Caucasian or Latino decent.Using a random effects model, we concluded that the Alu insertion was not associated with the risk of breast cancer under the dominant genetic model; the pooled OR was 1.025 (95% CI = 0.526–1.994, PGR gene and the incidence of breast cancer.Our meta-analysis showed that the Alu-insertion progesterone receptor gene polymorphism was not associated with breast cancer. These results provide further information regarding the association between the Alu insertion in the  Breast cancer is the leading cause of cancer-related deaths in women worldwide; globally, approximately 1 million women experience breast cancer each year . CurrentPGR gene, is a member of the steroid receptor superfamily. The progesterone receptor is essential for mediating the effects of progesterone, which is critical for the establishment and maintenance of pregnancy. Intracellular PGRs and their associated protein kinase C molecules are known to regulate tumor cell proliferation and metastasis, such as during the infiltration process of human glioblastomas [PGR that effect its level of expression may be associated with variations in the risk of breast cancer. Several reports have attempted to address the relationship between PGR expression and breast cancer risk in populations of various ethnicities, although with mixed results [The human progesterone receptor, encoded by the lastomas . Moreovelastomas . In addilastomas . Signatulastomas . Therefo results –14.PGR gene, in intron G between exons 7 and 8. The Alu insertion contains a half-ERE/SPI site, which may disproportionately increase the transcription of PGR after estrogen stimulus [The Alu element, a short interspersed nuclear element, is the most successful retrotransposon in primate genomes; it exists at an estimated copy number of 1.1 million in the human genome . Each Alstimulus . Some ststimulus , 23, whistimulus –26.These conflicting results are likely due to the limited sample size found in the studies as well as differing genetic backgrounds. Meta-analysis is widely-used in medicine as a statistical method of reconciling studies with inconsistent results . TherefoWe searched three online electronic databases  in order to identify potential studies for inclusion in our meta-analysis; the data of the last search update was November 2016. We used the following key words in our literature searches: progesterone receptor, PROGINS, Alu insertion, breast cancer, and mammary. Articles cited by the potential studies and relevant review articles were also checked for additional supplementary studies. The following inclusion criteria were utilized: (1) a case-control study design; (2) patients with a diagnosis of breast cancer; and (3) inclusion of the allele and/or genotype frequencies. In cases where studies included the same or overlapping data, we chose the most recent article. The corresponding authors were contacted for other useful information (such as sample characteristics) and additional data not presented in the initial article.Two researchers (Jun Yao and Xing-ling Qi) independently collected the relevant data, from all eligible publications. If there was a disagreement, a consensus was obtained after discussion. The following characteristics were collected from each study chosen for inclusion: first author’s last name, publication year, region, ethnicity, numbers of each genotype of both cases and controls, and source of controls.p < 0.05 was considered statistically significant.Our meta-analysis was completed using Stata version 10.0 . We used a chi-square test to determine the Hardy-Weinberg equilibrium (HWE) of each genotype frequency in control subjects. Thakkinstian’s method was used to calculate pooled frequency analyses . All sta1 (AA vs. aa), OR2 (Aa vs. aa), and OR3 (AA vs. Aa); these pairwise differences were used to select the most appropriate genetic model under the instruction as previously described [In order to measure the strength of the association between breast cancer and the Alu insertion, we calculated odd’s ratios (ORs) with 95% confidence intervals (Cis). We used a random effects model to pool the effect sizes across studies. This model measure the possible effect size across populations with different genetic backgrounds after considering the heterogeneity among the included studies . An alleescribed , 30.p > 0.05 indicated a lack of heterogeneity and p < 0.05 indicated the presence of heterogeneity [2 was the proportion of detected variation in effect size due to the actual discrepancies across studies; classically, the I2 statistic is used to define low (< 25%), moderate (~ 50%), and high (> 75%) levels of heterogeneity [We also determined the degree of heterogeneity across studies using the Q-statistic; ogeneity , 32. I2 ogeneity . We alsop < 0.05 was considered significant publication bias [We used a funnel plot to estimate publication bias. The standard error of log(OR) for each study was plotted vs. its log(OR); asymmetric plots indicated potential publication bias. The degree of asymmetry was measured using Egger’s test; ion bias .Finally, we performed sensitivity analyses to measure the potential influence of each study on the final pooled effect size as previously described .p = 0.0390) [After excluding published works with overlapping data and those that did not meet inclusion criteria, the final meta-analysis included a total of nine published articles containing 10 studies including 2106 cases and 1660 controls , 36–39 ( 0.0390) .Fig. 1St1/T1 represents homozygote individuals lacking the 306 bp Alu insertion, T1/T2 represents heterozygotes with the insertion, and T2/T2 indicates homozygous individuals with the Alu insertion. The allelic frequency of the Alu insertion varied across ethnicities: the pooled T2 allele frequency was highest among Indians , followed by Caucasians , Latinos , African-Americans , and Indo-Europeans . The overall pooled T2 allele frequency was 12.6% (95% CI = 7.4–17.8%).We calculated the pooled frequencies of the Alu insertion in the control populations stratified by ethnicity. Tp = 0.943). Ethnicity subgroup analysis indicated that the Alu insertion was associated with breast cancer in Indian  and Indo-European patients , but no association was found in Caucasians  or Latinos  .The association between the Alu insertion and the risk of breast cancer was determined in all 2106 cases and 1660 control subjects from 10 studies using pooled ORs and the corresponding 95% CIs for the homozygous codominant, heterozygous codominant, dominant, recessive, and allele contrast genetic models Table . FinallySensitivity analysis was conducted to measure the influence of each study on the resulting meta-analysis. The relevant pooled ORs indicated that no significant change appeared when each study was omitted, one at a time, from the overall meta-analysis. Thus, the final pooled results are both stable and reliable.p = 0.889).The potential publication bias was evaluated using a funnel plot Fig. . An EggePGR gene polymorphism  and the occurrence of breast cancer. Overall, the results of our meta-analysis provide evidence that the presence of the Alu insertion is not associated with an increased risk of breast cancer. Subgroup analyses by ethnicity or source of controls were used to investigate potential disequilibrium in the distribution of cases and controls. We also performed a sensitivity analysis, which reinforced the validity of the results.Our meta-analysis included 10 studies, comprised of 2106 cases and 1660 controls, that investigated the association between PGR variation and breast cancer varied across different populations. The Alu insertion was related to breast cancer in both Indians and Indo-European mixed racial groups, while this association disappeared in Caucasians and Latinos. This difference in association is likely due to two factors. First, the various genetic backgrounds of the racial groups may contribute as the frequency of the Alu insertion varies across different populations. Certainly, genetic factors confer higher risk levels for breast cancer [Associations between t cancer . Howevert cancer . In the PGR gene is not yet clear, it has been reported that the insertion might cause abnormal gene transcription and weaken the binding of progesterone to the PCR, which would subsequently reduce the activity of progesterone [Although the exact biological role of the Alu insertion into the esterone . TherefoFinally, there are several potential limitations of our study. First, there was measurable heterogeneity in the overall meta-analysis as well as in the sub-group analysis, which suggests that the underlying factors might partially contribute to the observed heterogeneity. Second, it is possible that the sample size was not large enough to generate a meaningful conclusion. Limited sample sizes are usually accompanied by selection bias. Thus, pooled results based on limited studies lack sufficient power to support or deny an association . Third, PGR gene is not associated with the risk of breast cancer. More studies with larger sample sizes will be needed to validate our findings and to explore potential epigenetic mechanisms and environmental influences on the risk of breast cancer.In conclusion, our results suggest that Alu insertion into the


FERMT2 gene as a new susceptibility locus for late-onset Alzheimer's disease (LOAD). In order to validate the association of the rs17125944 polymorphism with LOAD risk in the northern Han Chinese, we recruited a case–control study of 2338 Han Chinese subjects (984 cases and 1354 age- and gender-matched controls). Our results demonstrated that there was no significant association between the rs17125944 polymorphism and LOAD . Furthermore, no significant differences were observed in alleles and genotypes distribution after stratification by apolipoprotein E (APOE) ε4 and multivariate logistic regression analysis. We also performed a meta-analysis in 81908 individuals. The meta-analysis showed that the C allele is the risk factor for LOAD in Caucasian group  and combined population . While in Chinese population, the C allele is not associated with increased risk of LOAD . In conclusion, our study showed that the rs17125944 polymorphism in FERMT2 gene might not be association with LOAD in northern Han Chinese population.A recent meta-analysis of genome-wide association studies (GWAS) in population of Caucasian identified a single nucleotide polymorphism (SNP) rs17125944 in the  ABCA7, CLU, CR1, CD33, CD2AP, EPHA1, BIN1, PICALM, and MS4A [Alzheimer's disease (AD), as a progressive neurological disorder, is a major form of dementia in the elderly. Its two pathological hallmarks in brain are extracellular amyloid plaques, which are deposits of amyloid β (Aβ) peptide, and intracellular neurofibrillary tangles (NFTs), which are formed by the microtubule-associated protein tau . Late-onand MS4A . Recentland MS4A .FERMT2 (as known as kindlin-2) is a member of kindlin protein family, which also contains kindlin-1 and kindlin-3 [FERMT2 also promotes breast cancer progression through activating genome instability [FERMT2, were found to modify Tau toxicity [FERMT2 may be related to LOAD risk by influence Tau-mediated pathological process. The single nucleotide polymorphisms (SNP), rs17125944 in the FERMT2 gene on chromosome 14q22.1 was firstly found to be associated with LOAD in the completion of meta-analysis with 74,046 individuals from Caucasians. As a new susceptibility locus, rs17125944 reached genome-wide significance in the combined discovery and replication analysis [FERMT2 gene and LOAD risk in northern Han Chinese to validate the possible genetic association. We also conducted a meta-analysis of present association studies in different ethnic groups to detect the relationship between rs17125944 polymorphism and LOAD risk.indlin-3 . Kindlinindlin-3 , 8. A stindlin-3 , 10. FERtability . In recetoxicity . This reanalysis , and Xiaanalysis . Since tanalysis , it was P < 0.001, OR = 2.422, 95%CI = 1.970-2.977). Distributions of genotypes in AD patients and control subjects were in the Hardy-Weinberg equilibrium (P > 0.05).The demographic and clinical characteristics of the study participants are presented in Table P = 0.953; allele P = 0.975, OR = 0.998, 95% CI = 0.868-1.146). Then we stratified these data through the presence/absence of the APOE ε4. However, no significance was observed in both subjects with APOEε4 allele  and without the APOE ε4 allele . Furthermore, by multivariate logistic regression, there was also no association between the rs17125944 polymorphism and LOAD  after adjusting for age, gender, and the APOE ε4 allele carrier status  of these studies is not notable. While in Chinese population, the C allele is not associated with increased risk of LOAD .Following the search strategy, we got 4 studies, which met the inclusion criteria Figure . IncludiFERMT2, as known as kindlin-2, participates in integrin activation and cell-cell and cell-matrix adhesion [FERMT2 can modulate Tau toxicity [FERMT2 might play a role in the pathological process of AD through Tau-mediated neuronal injury. In 2013, a meta-analysis of 74 046 samples reported by the International Genomics of Alzheimer's Disease Project (IGAP) firstly found the susceptibility loci rs17125944 in FERMT2 gene for LOAD [adhesion . A studytoxicity . It sugghttp://www.ncbi.nlm.nih.gov/projects/SNP). Meanwhile, multiple genes and environmental factors and gene-environment interactions may affect LOAD risk [Our study failed to replicate the association in the northern Han Chinese. There might be some reasons for the replication failure. First of all, different genetic backgrounds between Han Chinese and European ancestry may lead to the opposite results. There is significant difference on the minor allele frequency (MAF) of rs17125944 between Chinese and Caucasians. The MAF of rs17125944 is 24% in Chinese, while the MAF of rs17125944 is 8.0% in Caucasians based on the dbSNP database . Xiao et al. discovered that rs17125944 is associated with LOAD risk  in Southern Han Chinese; however, Jiao et al. and our study did not replicate the relationship between rs17125944 and LOAD risk in other Chinese cohorts [Secondly, the meta-analysis in Chinese showed that the rs17125944 polymorphism has no significant association with LOAD  but with a moderate heterogeneity  and 1354 healthy control subjects , which were matched for age and gender. All the participants were Northern Han Chinese. The patients of LOAD were recruited from the Department of Neurology at Qingdao Municipal Hospital, and several other hospitals in Shandong Province. The probable AD was clinically diagnosed on the basis of the criteria of National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) by at least two neurologists . None ofTM kit  [DNA was extracted from the peripheral blood of participants using the Wizard genomic DNA purification kit  . The rs1, China) . And thet-test or the Chi-square test. Genotype and allele distributions were compared using the Chi-square test. Differences in allele and genotype distribution between cases and controls were analyzed using logistic regression adjusted for non-genetic covariates and APOEε4 status under various genetic models that were defined as 1(TC + CC) versus 0(TT) for dominant, 1(CC) versus 0(TT + TC) for recessive, and 0(TT) versus 1(TC) versus 2(CC) for additive. The p value, odds ratios (OR) and 95% confidence intervals (CI) were accounted. The statistical analyses were performed by SPSS 16.0 software. The criterion for significant difference was P < 0.05.The Hardy-Weinberg equilibrium (HWE) was calculated for SNP using genotype data from AD patients and controls. Differences of the characteristics between cases and controls were examined using the Student FERMT2 and LOAD, we performed a systematic literature search on PubMed, EMBASE and the Cochrane library using terms “FERMT2” or “fermitin family member 2,” “rs17125944,” “polymorphism,” and “Alzheimer's disease” or “AD.” The upper date was limited before February 2016. Since the restriction of language, only English articles were involved. And only the primary articles were included.In order to find all the articles about investigating the association between All the studies included should meet the following criteria: (1) assessing the relationship between rs17125944 and AD; (2) case-control studies; (3) NINCDS-ADRDA as the diagnostic criteria of AD; (4) support odds ratio (OR) with 95 % confidence interval (CI) or can calculated by sufficient data in studies.Following the inclusion criteria, data in available studies was extracted by two authors. We extracted the allelic odds ratio (OR) and 95% confidence intervals (CI), which were calculated by a logistic regression model. We also extracted other information, including author's name, publication year, ethnicity, numbers of cases and controls, proportion of female, mean age at onset in cases and mean age at examination in controls.2I estimates (2I < 50% as “lack of heterogeneity”). All the statistical analyses were conducted by Stata 12.0 software.The summary statistics from studies were combined by random effects (I-V heterogeneity) meta-analysis. Using the random (I-V heterogeneity) model, the pooled effect was estimated. The heterogeneity was calculated by with