Telephone-CPR (T-CPR) can increase rate of bystander CPR as well as CPR quality. Instructions for T-CPR were developed when most callers used a land line. Telephones today are often wireless and can be brought to the patient. They often have speaker function which further allows the rescuer to receive instructions while performing CPR.We wanted to measure adult lay people’s ability to activate the speaker function on their own mobile phone.Elderly lay people, previously trained in CPR, were contacted by telephone. Participants with speaker function experience were asked to activate this without further instructions, while participants with no experience were given instructions on how to activate it. Participants were divided in three groups; Group 1: Can activate the speaker function without instruction, Group 2: Can activate the speaker function with instruction, and Group 3: Unable to activate the speaker function. Time to activation for group 1 and 2 was compared using Mann-Whitney U-test.Seventy-two elderly lay people, mean age 68 ± 6 years participated in the study. Thirty-five (35)% of the participants were able to activate the speaker function without instructions, 29% with instructions and 36% were unable to activate the speaker function. The median time to activate the speaker function was 8s and 93s, with and without instructions, respectively (p < 0.01).One-third of the elderly could activate speaker function quickly, and two-third either used a long time or could not activate the function. Most out-of-hospital cardiac arrests (OHCAs) occur in adults above 50 years old ,2. In 90Instructions by emergency service dispatchers to start CPR and to improve quality of CPR via telephone (T-CPR) were first initiated in King County in 1983 , and resInitial dispatcher instructions were developed when most callers used a land line as illustrated in the Norwegian guidelines 2005 -17. UsinToday, most people in the developed world and a rapidly increasing portion in developing countries have a mobile phone. The first hand-held portable cell phone was presented in 1973, and the pocket version of mobile phones was developed and introduced in the late 80’s. As more and more functions were added to mobile phones, Nokia introduced their speaker function in the 90’s and today this is standard on most mobile phones.In a pilot study, we found that 30 of 35 lay people between 16 and 60 years old were able to activate the speaker function within 5 s without instructions . We wantObservational study of older adults with their own mobile phones.One hundred and thirty-one (131) volunteers aged 50 years and older who had attended CPR training in 2008 and signed up or participated in a CPR research study in 2009 ,23, accehttp://audacity.sourceforge.net). The researcher asked “Have you ever used the speaker function on your mobile phone?” If “yes”, the researcher continued “Would you please activate the speaker function now (t0) and tell me when it’s done?” If “no”, the researcher gave the following brief instructions: “Let’s try this together, I’ll help (t0) you. Look at the screen. Do you see a symbol for speaker function or the word speaker? If so, press on the symbol or the button that is closest”  or median  as appropriate. We also tested if there was any association between more advanced age and ability to activate speaker phone by a Chi-square test of proportions above and below the median age of 69. SPSS ver. 20  was used for statistical analysis.Seventy-two (72) of 74 people contacted, completed the study with mean age 68 ± 6 years Table . One parTwenty-five 25) of 72 35%) participants managed to activate the speaker function without instructions and 21 (29%) with instructions, with median times 8 s  and 93 s5 of 72 (5% particSix (6) of 21 participants who needed instructions (Group 2) and four in the group that never managed to activate speaker function (Group 3), unintentionally hung up and had to be called back to repeat the test  protocols the mean delay before first compression was four minutes in 519 cardiac arrest calls even after instructions regarding pulse check and mouth-to-mouth ventilation had been removed.  These reIt is unknown if time spent on instructions to activate the speaker will delay first compression. The present results indicate that a delay is likely in elderly callers not familiar with the activation technique. On the other hand, once continuous speaker phone communication is established, it is possible that dispatcher and rescuer collaborates better and are able to initiate CPR faster. This should be further investigated. The balance between potential delays to first chest compression versus the benefit of improving CPR quality is also unknown.Hauff reported that 47% of actual bystanders were in age group 36-65, and 41% in age group >65 [In our study, only one or two operations were necessary to activate the speaker function, and the procedure was not unified between the different phone models. A future option could be that the dispatcher can remotely put the callers’ phone on speaker. This would ensure speaker activation, eliminate time expenditure and mitigate the risk that callers unintentionally hang up, which happened in 14% of our cases. It would also help those who are unable to read the display due to small letters (or symbols), impaired sight, or bright light conditions. A concern associated with speaker phone option is background noise and impaired communication. As single-rescuer situations in a home are the most common for sudden out-of-hospital cardiac arrests , the bacCurrent dispatcher protocols do not include speaker function activation , but it Although introduced already in 1984 , currentCPR training materials and dispatcher protocols should actively consider how best to incorporate the speaker mode into telephone CPR instruction, allowing rescuers to receive instructions and help from the dispatcher and provide CPR at the same time.Campaigns may be used to highlight the potential of this functionality and how it can be activated. This may encourage people to become familiar with their own speaker function and become confident using it when calling medical emergency response.The phone models used by our participants had different procedures to activate the speaker function. Manufacturers should agree to simple and unified steps to make it easier for dispatchers to instruct the rescuer to activate the speaker and for people to become confident using it.Our study was performed in a controlled environment, without induced stress. As real situations can be stressful, pressing the wrong button and disconnecting with the dispatcher is probably more likely to happen.Our study population was previously CPR trained, and may perform better in general than the average caller, although activation of speaker function was not part of their previous training or testing.The mobile phone needs to be readily available to be used in an emergency situation. We did not ask our participants where they normally kept their mobile phone, but this should be further investigated.In our study there was no significant difference between time to activation of speaker function associated with increased age, gender nor mobile phone brand. However, we cannot exclude the possibility for a type II error and neither that a larger sample might allow for multivariate analysis of other factors that might predict the ability to activate speaker function.We only tested the ability to activate the speaker function, and did not continue with dispatcher-assisted telephone-CPR. This should be further investigated to learn more about how dispatcher-rescuer teamwork can improve the quality of bystander CPR.Elderly lay people with mobile speaker function experience activated the function quickly. Elderly without such experience either used long time or could not activate speaker function.Birkenes receive research scholarships provided by the Norwegian Research Council. Birkenes and Myklebust are employees at Laerdal Medical. Kramer-Johansen receives financial research support from Laerdal Medical. The study was sponsored by Laerdal Medical, Stavanger, Norway.All authors participated in the study design. TSB and HM collected the data; TSB performed the statistical analysis and drafted the manuscript. All authors have critical reviewed the manuscript, and the study was supervised by JKJ. All authors read and approved the final manuscript.


PTPN22, TNFA and MIF genes in a well-characterized cohort of children with JIA.Although more than 100 non-HLA variants have been tested for associations with juvenile idiopathic arthritis (JIA) in candidate gene studies, only a few have been replicated. We sought to replicate reported associations of single nucleotide polymorphisms (SNPs) in the PTPN22 C1858T (rs2476601), TNFA G-308A, G-238A  and MIF G-173C (rs755622) in 647 JIA cases and 751 healthy controls. We tested for association between each variant and JIA as well as JIA subtypes. We adjusted for multiple testing using permutation procedures. We also performed a meta-analysis that combined our results with published results from JIA association studies.We genotyped and analyzed 4 SNPs in 3 genes: PTPN22 variant showed only modest association with JIA , it demonstrated a stronger association with the RF-positive polyarticular JIA subtype . The MIF variant was not associated with the JIA as a whole or with any subtype. The TNFA-238A variant was associated with JIA as a whole , and demonstrated a stronger association with oligoarticular JIA  that was significant after correction for multiple testing. TNFA-308A was not associated with JIA, but was nominally associated with systemic JIA  and enthesitis-related JIA . Meta-analyses confirmed significant associations between JIA and PTPN22  and TNFA-238A  variants. Subtype meta-analyses of the PTPN22 variant revealed associations between RF-positive, RF-negative, and oligoarticular JIA, that remained significant after multiple hypothesis correction .While the PTPN22 and TNFA G-308A. By performing subtype analyses, we discovered a statistically-significant association between the TNFA-238A variant and oligoarticular JIA. Our meta-analyses confirm the associations between TNFA-238A and JIA, and show that PTPN22 C1858T is associated with JIA as well as with RF-positive, RF-negative and oligoarticular JIA.We have confirmed associations between JIA and  Juvenile idiopathic arthritis (JIA) refers to a collection of chronic autoimmune arthropathies in children. Although the etiology of JIA is complex, substantial evidence supports the importance of genetic factors in susceptibility to JIA -3. WhilePTPN22 (C1858T) has been consistently associated with JIA [MIF (G-173C) and TNFA  genes have also been associated with JIA, although some of the studies show mixed results [STAT4, TNFAIP3, IL2RA, and CCR5, and have failed to find an association with CTLA4 variants [TNFA and MIF loci in an independent JIA cohort and then to combine these results with published results in a meta-analysis. Furthermore, since prior studies of the PTPN22 variant have investigated combined JIA cohorts, we sought to investigate associations between JIA categories and the PTPN22 variant by meta-analysis.In previous non-HLA genetic association studies, a functional variant at with JIA ,10-12. V results -21. The  [MIF G-13C and TNCases were 647 children with JIA from Pediatric Rheumatology clinics at the University of Utah  and Emory University (N = 210 cases). Patients were diagnosed according to the ILAR criteria . The medPTPN22 locus, rs1800629 (G-308A) and rs361525 (G-238A) in the TNFA locus and rs755622 (G-173C) in the MIF locus. These variants were chosen because of their reported associations with JIA in more than one cohort based on a review of published literature [DNA was isolated from peripheral blood using the Puregene DNA purification kit from Qiagen . Subjects were genotyped for four SNPs in three loci: rs2476601 C1858T) in the terature -18,25-3158T in thp < 0.05) but subsequently adjusted for multiple comparisons using a permutation procedure. Our permutation procedure generated 1000 datasets under the null hypothesis of no association between JIA and genotype by repeatedly shuffling the vector of genotypes for each subject in the dataset. This type of permutation procedure preserves both the linkage disequilibrium among variants and the known effects of gender on JIA. We carried out all analyses using the R programming language [Prior to association analysis, we first tested whether each variant was in Hardy-Weinberg equilibrium (HWE) in controls. We then tested for association between each variant and disease outcome using a logistic regression model assuming an additive model of allelic effect and adjusting for gender. From such models, we calculated allelic odds ratios (OR) and 95% confidence intervals (95% CI) that were adjusted for gender. Since these variants have been previously implicated in susceptibility to JIA and other autoimmune disorders, we considered JIA to be the primary disease phenotype. However, since JIA is a collection of several heterogeneous subtypes, we repeated the analyses for specific JIA subtypes based on ILAR criteria. Since each of these variants has been previously implicated as being associated with JIA, we initially focused on nominal significance . Using allele frequency data derived from these studies, we performed meta-analyses of s Q test ,34. Whens Q test .MIF genotypes, 28 were missing PTPN22, 10 were missing TNFA238, and 40 were missing TNFA308 yielding genotyping success rates ranging between 97.2% to 99.3%.We found that all four SNPs were in approximate HWE in our controls, using the Bonferroni-adjusted alpha threshold of 0.0125. In our cohort, we removed 1 of the 647 cases missing gender information. Furthermore, we found that 17 individuals were missing genotype data at PTPN22 1858 T variant showed a nominal association in our JIA cohort  (Table p = 0.0041) and oligoarticular JIA  , p < 0.0001 .The ns Table  [6,8,10-p < 0.0005, p = 0.0007 and p < 0.0005, respectively) . Cochran’s test for heterogeneity was significant (p = 0.04), however, because the Donn et al. study including subjects from the United Kingdom [MIF and JIA than the other studies (Table p = 0.15)  ; no other subtypes were significantly associated with this SNP (Table TNFA-238A was the strongest association found in this study and remained significant after adjusting for multiple hypothesis testing using permutation resampling (corrected p = 0.0113). While the TNFA-308A showed no association with the entire JIA cohort, there was a nominal association between this SNP and systemic JIA  and ERA  (Tables 5) Table . Upon stTNFAG-238A variant [TNFAG-308A variant [TNFA variants in Turkish and Czech cases and controls; the others studied Western European populations [TNFAG-238A in Ozen et al.’s sample was 0.27 (vs. 0.03 for other studies) and MAF was 0.31 (vs. 0.11) for TNFA G-308A , and hence the meta-analyses were repeated after excluding the study   and controls (N = 750). Although the standard deviation increased with decreasing sample sizes, point estimates remained approximately identical for all analyses, indicating that between -site heterogeneity does not to appear to be a concern in our study. Results of these analyses can be seen in Additional file  and contTNFA G-238A and TNFA G-308A variants among European subjects [TNFA G-238A and JIA, and in particular oligoarticular JIA (significant after correction for multiple testing). Our meta-analysis also supported an association between this variant and JIA. As previously reported by Lee et al., we also did not find an association between JIA and TNFA G-308A[PTPN22 C1858T and MIF C-173G variants [PTPN22 C1858T and JIA, we did not confirm the association with the MIF C-173G variant. There are several possible explanations for the discrepancies observed. First there might be true differences between the different populations being evaluated. Second, by the addition of almost 1400 subjects, our meta-analysis benefited from improved power. Third, the studies included in the meta-analyses varied somewhat. For instance, Lee et al. chose to include a study by Hohler et al., which investigated an association between TNFA G-238A and juvenile psoriatic arthritis and psoriasis [PTPN22 C1858T from the study by Thompson et al [PTPN22 C1858T to be 0.143/0.094 and 0.149/0.095 for the initial and replication cohorts respectively (Tables Other meta-analyses between JIA and these variants have been published recently ,42. Lee subjects . In contFA G-308A. Based osoriasis . We did on et al . were suPTPN22 is associated with JIA. Our study also demonstrates the increased power of meta-analysis, and demonstrates that the PTPN22 C1858T variant is particularly associated with RF-negative, RF-positive and oligoarticular JIA categories, but not with ERA or systemic JIA. PTPN22 C1858T variant has been identified as an underlying risk factor for several different autoimmune phenotypes [TNFA-238A, supporting future investigations of the TNF-α pathway in JIA.In conclusion, our study provides convincing, replicated evidence that enotypes ,44,45. OThe authors declare that they have no competing interests.MK, MRP, AW, MRB carried out the DNA extraction and genotyping of the subjects. LP recruited participants and organized participant data. SAH, KRS, LBV, JFB recruited subjects and supervised phenotypic data collection. KAB, MPE, KNC, SLG, and LBJ participated in the analysis of data and interpretation, and helped draft the manuscript. SP conceived of the study, participated in its design and coordination, recruited participants, and helped draft the manuscript. All authors read and approved the final manuscript.Meta-analyses performed allowing for random study effects.Click here for filePTPN22, TNFA and MIF variants and JIA, including only Utah samples in analyses.Case-control analysis of Click here for fileResults of case-control association of PTPN22, MIF and TNFA variants among JIA sub-phenotypes, including only Utah samples in analyses.Click here for file


CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p = 0.018). Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone is being used.Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ). Pioglitazone is approved for use in the management of type 2 diabetes mellitus (T2DM), but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes  Pioglitazone (PIO) is the most widely used thiazolidinedione (TZD) anti-diabetic drug. The first TZD, troglitazone, was approved for clinical use by the United States Food and Drug Administration (FDA) in 1997  to improve insulin sensitivity   will be evaluated; because the data with PPARG are inconsistent, we conducted a meta-analysis to estimate the association between the best studied PPARG polymorphism and pioglitazone response. Finally, future research directions and methods to incorporate current pharmacogenomic findings in clinical practice are proposed.As more benefits and risks of PIO have been reported, clinically relevant variability in response has also been noted  (“thiazolidinediones”[MeSH Terms] OR “thiazolidinediones”[All Fields]) AND (“pharmacogenetics”[MeSH Terms] OR “pharmacogenetics”[All Fields]) and (2) (“thiazolidinediones”[MeSH Terms] OR “thiazolidinediones”[All Fields]) AND  OR “genetic polymorphism”[All Fields] OR “polymorphism”[All Fields]). The numbers of articles found from the two searches were 33 and 91, respectively without any restrictions. The following searches were conducted with Web of Science: Topic = (pioglitazone) AND [Topic = (pharmacogenomics) OR Topic = (pharmacogenetics) OR Topic = (polymorphism)]. The original hit number was 84. The titles and abstracts were screened to include only clinical studies that investigated differences in PK or PD of PIO based on genetic polymorphisms in human participants. Articles only written in English were examined and meeting abstracts were not included in the summary. Sixteen full-text original research articles meeting our criteria and published in peer-reviewed journals were identified by our literature search.PPARG p.Pro12Ala polymorphism. The change in fasting plasma glucose (FG) from baseline was used as the primary outcome of interest because the definition of the responder phenotype was not consistent between studies. The data presented in the original articles were used. For the study by Bluher et al. . A test for heterogeneity  was conducted, and a fixed-effects model was used. The publication bias was checked   and rs10509681:A>G in exon 8 (p.Lys399Arg)  compared with *1 homozygotes (3.3-fold)  has also been studied. OATP1B1 is an uptake transporter located at the basolateral membrane of hepatocytes that facilitates drug entry into the hepatocyte  was observed . PPARG is the gene encoding PPARγ, a ligand-activated transcription factor that regulates glucose homeostasis  and in A1C  than patients without the variant allele  gene was investigated. PTPRD polymorphisms associated with T2DM in a genome wide association study in a Chinese Han population  gene has been studied in patients receiving PIO therapy. Adiponectin is an adipokine, a peptide hormone secreted from adipocytes, known to play an important role in insulin sensitization and fat β-oxidation   is another gene studied along with ADIPOQ polymorphism to explain PIO response variability. The ADIPOR2 gene is highly expressed at critical sites involved in glucose metabolism and activation of this receptor is known to increase fatty acid oxidation and adiponectin-mediated glucose utilization  gene in response to PIO was studied in a Japanese population. Resistin is another adipokine known to antagonize insulin  GG genotype was previously associated with T2DM susceptibility  S447X polymorphism has been studied with respect to PIO response. Lipoprotein lipase is the rate-limiting enzyme for the breakdown of lipoproteins rich in triglycerides  gene and methylene-tetrahydrofolate reductase (MTHFR) gene were reported, but the IMT was not significantly affected by polymorphisms in these two genes  and the MTHER 677T allele carriers    rs1468271 (p = 0.006), glycogen synthase 1 (GYS1) rs2287754 (p = 0.013), chemokine C-C motif ligand 2 (CCL2) rs3760396 (p = 0.015), oxidized low density lipoprotein receptor 1 (OLR1) rs2742115 (p = 0.015), and growth hormone releasing hormone (GHRH) rs6032470 (p = 0.023)  rs903361 (0.0003), pyruvate kinase (PKM2) rs2856929 (p = 0.002), ADIPOR2 rs7975375 (p = 0.007), uncoupling protein 2 (UCP2) rs660339 (p = 0.008), and apolipoprotein H (APOH) rs8178847 (p = 0.010) , *3CYP2C8 is the only genetic variant annotated for PIO treatment as level 3 evidence, which was defined as “annotation for a variant-drug combination based on a single significant (not yet replicated) or annotation for a variant-drug combination evaluated in multiple studies but lacking clear evidence of an association”(Whirl-Carrillo et al., CYP2C8 and SLCO1B1. The variant allele *3CYP2C8 is associated with higher PIO clearance, which results in reduced exposure to PIO in carriers of this allele. The alteration in PIO PK has clinical implications, and the relevant consequences with drug interaction are a concern. Thus, if an inhibitor, inducer or substrate of CYP2C8 is to be administered with PIO in known *3CYP2C8 carriers, closer monitoring may be warranted. For future studies of PIO, CYP2C8 genotyping is recommended to better understand the variability in response to PIO and to interpret data more clearly when *3CYP2C8 carriers are present in the study. This may be especially important because of racial differences in *3CYP2C8 allele frequency. The *3 variant has been the focus of clinical PK studies with PIO, but the functionality of other CYP2C8 variant alleles need to be further determined preferably in vivo because the discrepancy between in vitro and in vivo data have been shown with CYP2C8 activity. In contrast to CYP2C8, there is currently no evidence to suggest that genetic variation in drug transporters affects PIO disposition.Clinically relevant variability in pioglitazone response has been demonstrated, but the underlying factors contributing to variability are not well-understood. This hypothesis article summarizes current evidence on pioglitazone pharmacogenomics; current data suggest that genetic variation is indeed an important factor contributing to pioglitazone response. Thus, we posit a strategy incorporating pharmacogenomic information may provide a more rational approach to achieve optimal outcomes. According to PharmGKB (PPARG p.Pro12Ala. T2DM patients with PPARG p.Pro12Ala variant are likely to have better glycemic response with PIO. Thus, the PPARG p.Pro12Ala is a promising polymorphism and one that should be included in clinical models developed to predict a patient's response based on genotype. However, this polymorphism alone is unlikely to explain all of the variability seen among patients. Consequently, other genetic variants as well as clinical factors must be considered. Indeed, several polymorphisms were identified in other genes related to PIO pathways. However, it is difficult to make any firm conclusions, based on single studies reporting a significant association, especially if it is not known how the polymorphism affects the functionality of the coded protein. Similarly, the identified polymorphism may merely be in linkage disequilibrium with the true functional variant. Therefore, the data must be interpreted with caution. Validation or replication of the finding is necessary before the pharmacogenetic knowledge can be applied to patient care. To better explain the variability in response, gene-gene and gene-environment interactions should also be considered.The genetic polymorphism most widely studied to better understand variability in PIO PD is Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy. For example, developing a scoring system that incorporates both clinical and genetic factors may provide more clinical utility and make the pharmacogenetic evidence more accessible to clinicians who are unfamiliar with this field. This is important because the data from several genes suggest PIO pharmacogenomics has the potential to be an important means to better optimize therapy in patients with T2DM.http://www.frontiersin.org/journal/10.3389/fphar.2013.00147/abstractThe Supplementary Material for this article can be found online at: Click here for additional data file.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


MMP-9 gene leads to higher promoter activity. We therefore investigated whether this polymorphism predisposes to both PD and sporadic ALS (sALS). Samples from 351 subjects with PD and 351 healthy controls from two major cities in China were compared, while samples from 226 subjects with sALS were compared to the same number of controls from three centers in China. A possible association between the C(−1562)T polymorphism in the MMP-9 gene and PD or sALS was assessed by restriction fragment length polymorphism (RFLP) analysis. Our results show a significant association between the C(−1562)T polymorphism in the MMP-9 gene and risk of PD  as well as risk of sALS , supporting a role for MMP-9 polymorphism in the risk for PD and sALS.Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) share several clinical and neuropathologic features, and studies suggest that several gene mutations and polymorphisms are involved in both conditions. Matrix metalloproteinase-9 (MMP-9) is implicated in the pathogenesis of PD and ALS, and the C(−1562)T polymorphism in the  Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders whose etiology and pathogenesis are poorly understood. Nevertheless, various biochemical, environmental and genetic mechanisms have been proposed for both conditions Interestingly, numerous studies have described individuals who demonstrate a neurodegenerative ‘overlap’ syndrome, comprising idiopathic parkinsonism, dementia, and ALS Matrix metalloproteinases (MMPs) are proteases that remodel the extracellular matrix (ECM). Matrix metalloproteinase-9 (MMP-9), a major component of the basement membrane, may contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, PD and ALS by inducing neuronal death MMP-9 gene may affect susceptibility to the developing both conditions. Only few studies have examined this possibility, and the results have been inconsistent. The C(−1562)T polymorphism, in which the T allele shows higher promoter activity than the C allele These findings linking MMP-9 to PD and ALS suggest that polymorphisms in the MMP-9 gene predisposes to either or both conditions.Therefore, we investigated a series of Chinese patients with PD or sALS to determine whether the C(−1562)T polymorphism in the In our case-control study, 351 Chinese patients with sporadic PD and 351 healthy, ethnically matched control subjects were consecutively recruited from two movement disorder centers: West China Hospital, Sichuan University, located in southwest China; and the First Affiliated Hospital, Sun Yat-sen University, located in southeast China. Clinical diagnosis of PD was established by two independent movement disorder specialists according to accepted criteria Patients with sALS were recruited from three medical centers: the Department of Neurology, Third Hospital of Hebei Medical University, Hebei Province, located in north China; the Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangdong Province, in southeast China; and the Department of Neurology, West China Hospital, Sichuan University, located in southwest China. All patients satisfied the 2000 El Escorial criteria for definite or probable ALS, and all patients and controls were ethnic Han Chinese. The control sample was composed of unrelated healthy individuals matched by age and sex. The average age for ALS patients is 52.0±11.5 years, and for controls is 51.0±12.6 years. There are no significant differences between ALS patients and the controls in age and gender.Separate control groups were used for the PD and sALS patient groups because the average age and sex ratio of patients with PD were significantly different from those of patients with sALS. The protocol of this study was approved by the Ethics Committee of all participants: Sichuan University, Sun Yat-sen University and Hebei Medical University. All individuals gave informed consent in writing.5′-TTATCTCCATCTCACAGTCTCATT-3′ (sense) and 5′-TATTTTTGGGGGGTGTAGTATC-3′ (antisense). PCR reactions (25 µl) contained 0.1 µg genomic DNA, 10 pmol of each primer, 10 pmol dNTP, and 1.5 units of Taq polymerase , and standard PCR buffer. Amplification conditions were an initial denaturation at 94°C for 5 min, followed by 35 amplification cycles consisting of denaturation at 94°C for 30 s, annealing at 56°C for 30 s, and extension at 72°C for 30 s, with a final extension at 72°C for 5 min. All amplification reactions were resolved by 2% agarose gel electrophoresis to confirm the specific PCR products. These products were then digested overnight in a total volume of 10 µl at 37°C with the restriction endonuclease Sph I , separated on a 3% agarose gel and stained with ethidium bromide.Genomic DNA was extracted from peripheral blood leukocytes using the standard method of proteinase K digestion, followed by phenol-chloroform extraction and ethanol precipitation. Samples were genotyped for the C(−1562)T polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Amplified DNA was sequenced using the following primers: 2) analysis was used to assess differences in allele and genotype frequencies between patient and control groups. A Hardy–Weinberg equilibrium (HWE) program was used to test whether alleles deviated from HWE. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A two-tailed P-value <0.05 was considered significant. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) for Windows .Chi-square  and the corresponding control group (p = 0.808), as well as in the ALS group (p = 0.192) and the corresponding control group (p = 0.464). Because of the relatively low frequency of the TT genotype, we combined the CT and TT genotypes into the CT+TT group, which we compared with the CC genotype group  and heterozygous/homozygous genotype  for the C(−1562)T polymorphism T polymorphism in the pe group . And CC morphism .We then analyzed whether heterozygous and homozygous C(−1562)T carriers with PD or sALS differed in their clinical characteristics. Heterozygous and homozygous C(−1562)T carriers and non-carriers of C(−1562)T polymorphism with PD did not differ significantly in gender ratio, age at onset, onset symptoms, Hoehn-Yahr stage or United Parkinson’s Disease Rating Scale (UPDRS) . SimilarMMP-9 gene and risk of PD, and the first study to confirm a positive association between the C(−1562)T polymorphism and risk of sALS. In our hospital-based case-control study, we demonstrated that the C(−1562)T polymorphism is a potential risk factor for both PD and sALS in the Han Chinese population of mainland China. In fact, we found that the polymorphism increases the risk of PD by approximately 2.3-fold and of sALS by nearly 2.2-fold.To the best of our knowledge, this is the first report investigating the association between the C(−1562)T polymorphism in the MMP-9 gene and risk of sALS (p = 0.47). This discrepancy may be due to small population, to ethnic differences, and/or to genetic background, and should be confirmed in cohorts in other countries and in other ethnicities from Asian countries.These results contradict earlier observations in a Polish population involving 228 sALS patients In our study, although our results show no significant differences by statistics in gender in both PD group and ALS group, they indicate that there is a trend that more female cases carrying heterozygous CT and/or homozygous TT in PD group and more male cases carrying heterozygous CT and/or homozygous TT) in ALS group. This is an important found which would be helpful for further study. We speculate that the C(−1562)T polymorphism may have different roles in the Pathological mechanism of PD and ALS, though it is associated with the risk of both PD and ALS. Further studies based on large samples and multi-centers are needed to confirm these new discoveries.Although our results indicate an association between carriers and non-carriers of the C(−1562)T polymorphism and risk of PD and sALS, we did not find an association between C(−1562)T genotype and onset age, onset symptoms or severity of PD according to the Hoehn-Yahr stage and UPDRS. Similarly, we did not find an association between C(−1562)T genotype and onset age or onset symptoms of sALS.DCT1), which is involved in axon maintenance, have been strongly linked to Perry syndrome, which is a parkinsonian disorder with TDP-43-positive pathology; frontotemporal lobar degeneration (FTLD); and ALS ANG is a link between PD and ALS Our finding that polymorphism in a single gene predisposes to two neurodegenerative disorders adds to the number of cases in which genetic mutations have been linked to neurodegenerative disease. For instance, mutations in the dynactin1 gene  and Huntington’s disease (HD) Our study has shown, for the first time, that the C(−1562)T polymorphism is likely to constitute a risk factor for both PD and sALS in China. Although the sample size was moderate, which limited the statistical power of our study, the fact that subjects were recruited from distant regions of the country should improve our genetic coverage. Nevertheless, our results should be independently confirmed in larger-scale studies conducted in China and in other countries. Also, more studies should test samples on ANG gene, and the trinucleotide expansions ATXN2 gene in PD and ALS patients. In particular, future studies should ensure more adequate representation of women in the sample. Such studies should help elucidate the association of this polymorphism with the pathogenesis of PD and ALS.


The +49A/G polymorphism of the cytotoxic T-lymphocyte-associated antigen-4 gene (CTLA-4) has been associated with Graves’ disease (GD). However, results have been inconsistent. The aim of this study was to quantitatively summarize the evidence for CTLA-4 +49A/G polymorphism and GD. Electronic search of PubMed was conducted to select studies. Case-control studies containing available genotype frequencies of CTLA-4 +49 were chosen, and Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. Forty-two case-control studies including 8,288 cases and 9,372 controls were identified. Three studies were eliminated from the total 42 studies due to a p-value <0.05  in these studies which induced significant publication bias. The overall results suggested that the variant genotypes were highly associated (p<0.01) with GD risk in all genetic models . Similarly, in the subgroup analyses for ethnicity , the results were positive. This meta-analysis suggests that the CTLA-4 +49A/G polymorphism is highly associated (p<0.01) with increased risk of GD, especially in Caucasians and Asians. To validate this association, further studies with larger participants worldwide are needed to examine associations between this polymorphism and GD. GD is aet al , Marron l . Case-control studies containing available genotype frequencies of 49A/G were chosen. Additional studies were identified by a manual search of the references of the original studies.2 test. The strength of association between the +49A/G polymorphism of the CTLA-4 gene and GD was assessed by calculating crude odds ratios (ORs) with 95% confidence intervals (CIs). The pooled ORs were performed for the additive genetic model (G vs. A), dominant model (G/G+G/A vs. A/A) and recessive model (G/G vs. G/A+A/A), respectively. Heterogeneity assumption was checked by a χ2-based Q-test. A p-value of <0.05 for the Q-test indicated a lack of heterogeneity among the studies; the summary OR estimate of each study was calculated by the random effects model  .This meta-analysis examined the association of the CTLA-4 +49A/G polymorphism with GD and included 8,288 GD cases and 9,372 controls. Three studies were eliminated from the total 42 studies due to a p-value of <0.05  in these studies which induced significant publication bias. The results of Egger’s test provided statistical evidence for funnel plot symmetry . The overall results suggest that the variant genotypes were highly associated (p<0.01) with GD risk in all genetic models . Similarly, in subgroup analyses for ethnicity , the results were positive.GD is a disease with significant clinical consequences. The mechanism of GD is still relatively unknown. Although environmental factors, such as infection  and streThis meta-analysis revealed a highly significant (p<0.01) association between the CTLA-4 +49A/G polymorphism and GD risk, in both Asian and Caucasian subgroups. In conclusion, this meta-analysis suggests that the CTLA-4 +49A/G polymorphism is potentially associated with the risk of GD among Caucasians and Asians. Future, well-designed, large scale studies are necessary to validate this association in different populations.


Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity.The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HTHTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR). Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire . Sum score ≥20 was defined severe dyspepsia.Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment  were analysed. Patients were genotyped for HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia . This association appeared to be stronger in females  and patients homozygous for the long (L) variant of the 5-HTTLPR genotype . Females with 5-HTTLPR LL genotype showed the strongest association .HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms. These results support the hypothesis that diminished 5-HT3 mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.The  Dyspeptic symptoms are common in the general population, accounting for 3-8% of the consultations in general practice -3. AlthoH. pylori is likely underlying the associations with RANTES promoter C-28G genotype and Toll-like receptor 2 -196 to -174 del carrier status methyl-L-tryptophan trapping as a proxy for brain serotonin synthesis, showed a lower rate in healthy women compared to men [3 receptor mediated antinociceptive effects.The association between severe dyspeptic symptoms and the eceptors . Lack ofd to men . Althoug3 receptor with lower response to 5-HT due to polymorphism, rapid 5-HT re-uptake by 5-HTT and less serotonin available for receptor activation due to gender differences in 5-HT synthesis predisposes to increased perception of visceral stimuli. The influence of the HTR3A c.-42C > T genotype has also been evaluated in  patients with irritable bowel syndrome (IBS) [3 receptors on GABAergic interneurons innervating the amygdala exerts an inhibitory influence on amygdala reactivity, whereas those on excitatory interneurons have the opposite effect [3 receptors on GABAergic interneurons resulting in greater inhibition of the amygdala [3 receptor subunit composition may vary in the different regions of the central nervous system as well as the influence of 5-HT3 receptors on excitatory interneurons. Moreover, in dyspepsia increased amygdala responsiveness may be secondary to decreased spinal antinociception. It is noteworthy that another study in patients with IBS suggests that the HTR3A c.-42T allele is associated with the diarrhea-predominant phenotype of the disease [HTR3A c.-42T allele was found to be associated with visceral hypersensitivity in patients with gastroesophageal reflux disease [In short, the presence of a 5-HTme (IBS) . In contme (IBS) . Consistme (IBS) ,41. Actie effect . The finamygdala ,41 These disease . Patient disease . Further disease .HTR3A c.-42C > T polymorphism likely represents a predisposing genetic variant in common to psychiatric disorders and dyspepsia. Recently, effects of the HTR3A c.-42C > T genotype on emotional brain correlates of susceptibility to depression have been reported [HTR3A c.-42C > T polymorphism and anxiety in patients with dyspepsia.The reported . Furtherreported  and in Creported . Althoug3 receptor composition and function have been performed in vitro or in rodents, which lack expression of the HTR3C, D, and E subunits [3 receptors on spinal inhibitory interneurons. Also the consequences of increased expression of 5-HT3A subunits for receptor composition and antinociceptive function have not been assessed in vivo. Secondly, there is a possibility that association between HTR3A c.-42T allele and severe dyspeptic symptoms is due to the effect of some other polymorphism, even in another gene, which is in linkage disequilibrium with HTR3A c.-42C > T. Indeed, the serotonin receptor subunit gene HTR3B maps in close proximity to HTR3A and the possibility has been raised that the HTR3A c.-42C > T polymorphism is not the susceptibility variant but a common variant in HTR3B, found to be associated with depression in Japanese [HTR3A c.-42C > T and 5-HTTLPR polymorphisms with dyspeptic symptoms was detected in tertiary referral patients [To appreciate results of this study several limitations should be mentioned. To date, most studies on 5-HTsubunits . It is nJapanese . Furtherpatients . In the HTR3A c.-42T allele and severe dyspeptic symptoms. Altered 5-HT3 receptor function alone or in combination with 5-HTTLPR genotype could explain symptom severity in a subgroup of patients. The associations may be explained by the increased susceptibility to visceral hypersensitivity of the gastrointestinal tract and/or increased risk of having psychiatric comorbidity. Further research will have to replicate this result and clarify the clinical consequences of it.The results of this study suggest that there is an association between The authors declare that they have no competing interests.SM, NJW, CJM, GAJF, RJFL, JWMM, and MEN designed the study. SM, CJM, and GAJF obtained the blood samples and questionnaire data. Laboratory work was undertaken by SM and JJML. SM, JJML, NJW, DEG, and MEN analyzed the data and wrote the first draft of the paper. SM and CO carried out the statistical analysis. All authors contributed to and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/12/140/prepub


IRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD risk as well as the modulation of this association by some environmental and life-style factors. Genotypes were determined in DNA from blood of 269 AMD patients and 116 controls by the allele-specific oligonucleotide-restriction fragment length polymorphism and the polymerase chain reaction-restriction fragment length polymorphism. An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found . On the other hand, the G/A genotype reduced the risk of AMD as well as its dry or wet form . Moreover, the G allele of the g.49520870 G>A-IRP2 polymorphism increased the risk of the dry form of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66). Our data suggest that the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms may be associated with increased risk for AMD.Iron can be involved in the pathogenesis of AMD through the oxidative stress because it may catalyze the Haber–Weiss and Fenton reactions converting hydrogen peroxide to free radicals, which can induce cellular damage. We hypothesized that genetic polymorphism in genes related to iron metabolism may predispose individuals to the development of AMD and therefore we checked for an association between the g.32373708 G>A polymorphism (rs867469) of the  Age-related macular degeneration (AMD) is an eye disease that is characterized by progressive vision loss of variable severity accompanied by distinct changes in the structure of the retina, retinal pigment epithelium (RPE), Bruch’s membrane and choriocapillaris . CurrentAlthough the pathophysiology of AMD is not clearly understood, it is well accepted that both oxidative stress and genetic factors in combination with environmental and life-style factors play an important role in the pathogenesis of the disease. The most consistent major risk factor for AMD is age. The development of AMD is a slow progressive process that occurs with aging and mainly affects people over age 60 . While pAge-related disorders, including retinal diseases may result from cumulative oxidative damage resulting from reactive oxygen species (ROS) –13. The A number of epidemiological studies have implicated AMD as an inherited disease showing that family members are at an increased risk of the disease –20. ConsIRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD as well as the modulation of this association by some environmental and life-style factors. Both polymorphisms are SNPs with a minor allele frequency >3% in European population and are located in the 5′ flanking region of these genes. Polymorphism in this region can affect mRNA stability and degradation, and gene expression. , 0.2 mM of each dNTP, 1.5 mM MgCl2, 0.25 μM of each primers . The primers designed to detect the g.32373708 G>A SNP were as follows: allele-specific sense oligonucleotides 5′-TGCACACCTGCAAAGAAG-3′ for G variant and 5′-TGCACACCTGCAAAGAAA-3′ for A variant and antisense oligonucleotide 5′-CTAGATGAAAGGTGGTGAGG-3′. The allele-specific oligonucleotide-restriction fragment length polymorphism (ASO-PCR) conditions were as follows: 5 min of initial denaturation at 95°C, followed by 30 cycles of 30 s denaturation at 95°C, 30 s annealing at 56°C and 1 min extension at 72°C. The final extension step at 72°C for 5 min was also included. The PCR products (237 bp) were fractionated by electrophoresis on a 8% polyacrylamide gel, stained with ethidium bromide and viewed under UV light. Fig. The genotypes of the g.32373708 G>A-IRP2 polymorphism. PCR assay was performed in a total reaction volume of 25 μl containing the same chemicals as in the previous analysis except for primers. 360 bp length fragments containing polymorphic site were amplified using the following primers: sense 5′-CCCCCACTTGAAAACACG-3′ and antisense 5′-AGATCGTCGGACAGGAAAAC-3′. The PCR profile contained an initial denaturation step for 5 min at 95°C, 30 cycles at 95°C for 30 s, 30 s at 60°C annealing temperature and 60 s at 72°C and the final extension step for 5 min at 72°C. After amplification, the 360 bp PCR products were analyzed on a 3% agarose gel and digested with 3 U of BspTI (AflII) restriction endonuclease  in a final volume of 15 μl for 16 h at 37°C. PCR products with a G at the polymorphic site were digested into two 183 and 177 bp fragments, while those with A were not because of the absence of a BspTI (AflII) restriction site. The G/G genotype produced two fragments , whereas the G/A genotype produced three fragments  and the homozygote A/A resulted in only one fragment 360 bp. Digested PCR products were separated by electrophoresis on a 8% polyacrylamide gel and visualized by ethidium bromide staining using a GeneRuler ™ 100 bp  as a size marker. A representative gel for this polymorphism is presented in Fig. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the genotypes of the g.49520870 G>A-2 analysis was also used to test the significance of the differences between distributions of genotypes and alleles in AMD patients and controls. The association between case–control status and each polymorphism, measured by the odds ratio (OR) and its corresponding 95% confidence interval (CI), was estimated using an unconditional multiple logistic regression model, both with and without adjustment for sex, age, smoking habit, living environment , and family status of AMD. Smoking habit was categorized in terms of never smokers and smokers (including current and former). Stratified analysis according to age, sex, and family status of AMD was also conducted. To study a possible gene-environment interaction, the patients and controls were divided into subgroups depending on sex, family history and age. Unconditional logistic regression analyzes were also performed to assess the association between genotypes and risk for AMD after stratification of the individuals according to sex, age, and family status of AMD.All statistical analyzes were performed using STATISTICA 9.0 software  and SigmaPlot v11.0 software . To compare the distributions of demographic variables and selected risk factors between patients and controls Chi-square test was used. Hardy–Weinberg equilibrium (HWE) was checked using Chi-square test to compare the observed genotype frequencies with the expected frequencies among the case and control subjects. The χp < 0.001). Therefore, these variables were further adjusted in the multivariate logistic regression model to control for possible confounding factors of the main effects of the polymorphisms. Moreover, we explored the relationships between age, sex, smoking, living environment and family history of AMD and the risk of AMD independently of genotype. We compared AMD patients and controls according to these parameters (Table p = 0.024), age  and first-degree relatives with AMD  significantly increased the risk of the disease.The characteristics of the patients with AMD and AMD-free controls involved in this study are presented in Table rs Table . Our resIRP1 and g.49520870 G>A-IRP2 polymorphisms in AMD patients and controls are summarized in Table IRP2 SNP were all in agreement with the HWE calculated for the cases and controls . As shown in Table IRP1 SNP between the cases  and controls was statistically significant (p < 0.05). An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found . On the other hand, the G/A genotype reduced the risk of AMD as well as dry form of AMD or wet form of AMD, separately . Furthermore, in the dry form of AMD, the G allele of the g.49520870 G>A-IRP2 SNP increased the risk of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66).The genotype and allele distributions of the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms. The distribution of combined genotypes of these polymorphisms is shown in Table We also evaluated the associations between the occurrence of AMD and combined genotypes of the g.32373708 G>A-The presence of the A/A–G/A genotype of both polymorphisms increased the risk of AMD as well as its dry or wet form, separately , whereas the presence of the G/A–G/G genotype decreased such risk .Furthermore, the G/A–G/A genotype may have a protective effect against wet AMD and AMD . In the wet form of AMD and AMD, the G/G–G/A and A/A–G/G genotypes increased the risk of the disease .IRP1 and g.49520870 G>A-IRP2 polymorphisms in the group of wet AMD patients in comparison with dry AMD patients (data not shown). Such comparison was considered as a measure of AMD progression. We did not find any association between the progression of AMD and genotypes/combined genotypes and alleles of both polymorphisms.Additionally, we examined the distribution of genotypes/combined genotypes and alleles of the g.32373708 G>A-IRP1 are presented in Table The association between AMD and the tested SNPs was subjected to stratification analysis, but only data for the g.32373708 G>A-We showed that age, sex, and family status of AMD were significant risk factors in the development of AMD, which is in agreement with previous results obtained by others , 31. Howcis-regulatory RNA motifs—IREs located in the 5′ or 3′ untranslated regions (UTR) of mRNAs encoding proteins of iron uptake [transferrin receptor 1 (TfR1) and divalent metal transporter-1 (DMT-1)], export (ferroportin), utilization (5-aminolevulinate synthase) or storage (ferritin H- and L-chains) [IRP1 also known as the cytosolic aconitase (ACO1) has two mutually exclusive functions. When iron is abundant, IRP1 assembles an Fe–S cluster and has aconitase activity, whereas—when iron is scarce, the apoprotein without its Fe–S cluster acquires IRE-binding activity [IRP2 also called IREB2 (iron-responsive element binding protein 2) shares 79% homology with IRP1 but lacks aconitase activity [Although the pathogenesis of AMD is not completely understood, a growing body of evidence suggests that oxidative stress and free radical damage may mediate or exacerbate macular degeneration . Oxidati-chains) . In mammactivity . IRP2 alactivity . Mice wiactivity –48. In bactivity –51. The activity –54.BF; complement component 2, C2), 19p13.3–13.2  [IRP1 gene and the g.49520870 G>A polymorphism in the IRP2 gene increase the risk of AMD. To our knowledge, the g.32373708 G>A-IRP1 polymorphism and the g.49520870 G>A-IRP2 polymorphism have not been studied in AMD patients so far. We observed, for the first time, that the occurrence of AMD was positively correlated with the presence of the G/G genotype of the IRP1 SNP and of the G allele of the IRP2 SNP.Some results demonstrate that multiple genes and proteins are involved in development of AMD. AMD can be genetically associated with multiple susceptibility loci, i.a. 1q32 , 10q26 (ARMS2), 6p21.3  –61. As mt 3, C3) , 63. FurIRPs genes may be associated with development of AMD. These findings may be helpful in increasing our understanding of the etiology of AMD. Identification of genetic risk factors for AMD is the first step towards earlier detection and prevention, and in the future, better treatments.In conclusion, our work shows that genetic polymorphisms of the


CG + GG). Subgroup analysis by ethnicity showed that the IBD risk associated with the -173G/C gene polymorphism was significantly elevated among Asians , but not among Caucasians. Subgroup analysis by disease suggested that the -173G/C gene polymorphism is a risk factor for ulcerative colitis , but that it was not associated with Crohn’s disease. This meta-analysis suggests that the -173 G/C polymorphism in the macrophage MIF gene contributes to IBD susceptibility, specifically in Asian populations. Further studies are needed to validate these findings.The -173 G/C polymorphism in the macrophage migration inhibitory factor (MIF) gene has been implicated in susceptibility to inflammatory bowel disease (IBD), but the results are inconclusive. The present meta-analysis aimed to investigate the overall association between the -173 G/C polymorphism and IBD risk. We searched in Pubmed, and Embase for studies evaluating the association between the -173G/C gene polymorphism and IBD risk. Data were extracted and statistical analysis was performed using Revman 5.1 and STATA 12.0 software. A total of seven publications involving 4729 subjects (2282 IBD cases and 2447 controls) were included in this meta-analysis. Combined analysis revealed a clear association between this polymorphism and IBD susceptibility (OR = 1.48, 95% CI: 1.10–2.00,  Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), refers to a heterogeneous group of chronic disorders that leads to cachexia. IBDs are essentially incurable, are of unknown etiology and typically follow a clinical course featuring remissions and relapses . IncidenMIF is an important pro-inflammatory cytokine that plays a critical role in regulating immune and inflammatory response . Serum MA total of seven publications evaluating the association between the MIF -173G/C polymorphism and IBD risk were included in the meta-analysis, involving 4729 subjects (2282 IBDs cases and 2447 controls) –17. In pvs. CG + GG in order to choose the most suitable calculation model. Across all included studies, χ2 was 11.61 and p = 0.48 for a random-effects model, and I2, another index of heterogeneity, was 0%. These findings suggested a lack of heterogeneity. Thus, we chose the fixed-effects model to synthesize the data. The pooled OR based on all studies was 1.48 (95% CI: 1.10–2.00), which was associated with a Z value of 2.61 (p = 0.009)   . This su = 0.11) . These rp = 0.001).Subgroup analysis by ethnicity, showed that, among the studies involving Asians ,15,16, Cvs. CG + GG comparison genetic model, suggesting the absence of publication bias (p = 0.301).To assess the stability of our findings, sensitivity analysis was performed by sequentially excluding each study. Statistically similar results were obtained after sequentially excluding each study, suggesting the stability of the results. Begg’s funnel plot and Egger’s test were used to assess publication bias. The shape of the funnel plots seemed symmetrical for the CC ion bias . Then, EIBD refers to a group of chronic relapsing intestinal inflammatory diseases of unidentified causes. Taking epidemiological, genetic and immunological data together, indicates that IBD results from a complex interplay of genetic and environmental factors that produce an intestinal inflammatory response ,21. GeneA total of seven publications describing thirteen case-control studies in Asians and Caucasians were included in this meta-analysis. The effects of dominant/recessive models and of allele frequency were all estimated. In addition, the consistency of genetic effects across different ethnicities and IBD types was investigated. Our findings support the notion that, among Asians, the MIF -173G/C polymorphism plays a role in the development of IBD, and that the homozygotic CC genotype may be a risk factor for IBD.Our data indicate a strong ethnic bias in the association between the MIF -173G/C polymorphism and risk of IBD. We found the polymorphism to be a risk factor for IBD among Asians, with CC homozygotic carriers at higher risk of IBD than CG and GG homozygotic indivividuals. Among Caucasians, however, we found no evidence of an association between the MIF -173G/C polymorphism and risk of IBD. We also identified a disease-specific bias in the association. While we did not find any evidence of an association between the MIF -173G/C polymorphism and risk of CD, we did find that the polymorphism may be a risk factor for UC, suggesting that the associations between MIF -173G/C polymorphism and IBD risk are ethnicity and disease specific. These findings are consistent with a recent study suggesting that, although the etiology of CD and UC may overlap, the two diseases appear to have different genetic risk profiles .Our finding that the -173G/C polymorphism is a genetic risk factor for IBD in Asians but apparently not Caucasians, suggests population-specific genetic differences in IBD pathogenesis. Therefore, depending on the population, IBD may be associated with different genes, different loci within the same gene, and/or different polymorphisms at the same locus. Indeed, a systematic review of genes associated with susceptibility to IBD in Asian populations found that genetic risk factors differed between Asians and Caucasians . Those aFurther research is needed to examine not only the genetic risk factors of IBD, but the environmental risk factors as well. Based on available evidence, we cannot exclude the possibility that environmental risk factors explain at least part of the ethnic bias observed here in the association between the MIF -173G/C polymorphism and IBD risk. Therefore further work is essential to tease apart the relative contributions of genes and environment. In addition, to take consideration of population differences will be particularly informative, susceptibility genes identified in IBD patients with different ethnicities provide an opportunity to explore new mechanisms of disease that are specific in different population. What’s more, strongly suggesting that blockade of MIF bioactivities by either neutralizing anti-MIF antibodies or antagonists prevents an inflammatory cytokine cascade, which strongly suggests that targeting MIF may be effective for treating IBD . Thus, aThe findings in this meta-analysis should be interpreted with caution because of several limitations. First, a relatively small number of studies and subjects were included in this meta-analysis, which may reduce the statistical power for identifying possible associations between the MIF -173G/C polymorphism and IBD risk. In particular, the apparent lack of association between this polymorphism and disease risk in Caucasians and in patients with CD should be verified in larger-scale studies. Second, the included publications were limited to Asian and Caucasian populations, so future work should examine other populations, such as Latinos, especially given substantial evidence of ethnic bias in the -173G/C polymorphism. Third, although we did not set any language restrictions during our literature searching, we included only English-language publications in the meta-analysis. It is possible that our results would be different if they included the findings of unpublished studies or of relevant studies published in other languages.Two authors independently performed systematic searches of Pubmed and Embase databases in January 2013 to identify studies examining the association between the -173G/C polymorphism in the MIF gene and IBD risk. Search terms were as follows: “IBD or inflammatory bowel disease or Crohn’s disease or ulcerative colitis” in combination with “migration inhibitory factor” in combination with “polymorphism or variant or mutation”. The reference lists of identified studies and review articles were manually searched to find additional relevant publications.Studies were included in the meta-analysis if they satisfied the following inclusion criteria: (1) they evaluated the potential association between the MIF gene -173G/C polymorphism and IBD risk; (2) they were case-control studies; (3) genotype distributions were available for cases and controls in order to estimate an odds ratio (OR) with 95% confidence interval (CI); (4) the distribution of genotypes in the control group was consistent with Hardy-Weinberg equilibrium (HWE). Abstracts, reviews, and studies in which genotype frequencies were not reported were excluded; and (5) when publications involved the same or overlapping data sets, only the study with the largest number of participants was included.Two reviewers independently extracted data from the final set of included studies. The following data were extracted: the name of the first author, year of publication, country of origin, ethnicity, sample size, IBD diagnosis, genotyping method, and genotype frequencies in IBD cases and controls.Z-test and p < 0.05 was considered statistically significant. First, we evaluated the dominant model (CC + CG vs. GG) and recessive model (CC vs. CG + GG), followed by the additive model (CC vs. GG). We also estimated the association based on allelic contrast (C vs. G). To evaluate whether the association showed any ethnicity- or disease-specific effects, we analyzed the data for separate subgroups defined by ethnicity and diagnosis with CD or UC.The strength of the association between the MIF -173G/C polymorphism and risk of IBD was assessed using ORs and 95% CIs. The significance of the pooled OR was determined using the 2-based Q statistic and I2 statistic, with p < 0.10 considered statistically significant. When p ≥ 0.10, the pooled OR of each study was calculated using a fixed-effects model; otherwise, a random-effects model was used.Heterogeneity was evaluated using a χPublication bias was assessed using Begg’s funnel plots and Egger’s test ,27. SensTo the best of our knowledge, this is the first meta-analysis to assess the relationship between the MIF-173G/C polymorphism and IBD risk. Our results suggest that the -173G/C polymorphism is a risk factor for IBD in Asians but not in Caucasians. Large well-designed, multi-center epidemiological studies should be carried out in these and other ethnic populations to confirm our findings.


Mink gene S38G polymorphism in the β-subunit of slow activating component of the delayed rectifier potassium channel current potassium channel has been associated with increased atrial fibrillation (AF) risk. However, the individual studies results were still controversial. To investigate the association of Mink S38G gene polymorphisms with AF, a meta-analysis including 1871 subjects from six individual studies was conducted. Mink S38G gene polymorphism was significantly related to AF under allelic , recessive , dominant , additive , homozygous , and heterozygous genetic models . A significant association between Mink S38G gene polymorphism and AF risk was found. G allele carriers may predispose to AF. Its preancement .Mink gene is located in 21q22.1-22.2, spans about 390 bp, encodes 130 amino acids, and constitutes the Iks β-subunit. Lai et al. (2002) found that a Mink gene rs1805127 locus at the 112th base adenine (A) was substituted with a guanine (G) at the exon region, resulting in the wild-type Serine  being replaced by Glycine  at 38th amino acid in the 3rd exon. They also found that the Mink S38G gene polymorphism was correlated with AF [Mink S38G gene polymorphism with AF; however, the results were contradictory. Zeng et al. (2005) found that Mink S38G gene polymorphism was not associated with AF in a study conducted with Beijing Chinese population [Mink 38G allele was significantly correlated with AF in a study conducted with Chongqing Chinese population [Several studies have associated pulation .Mink S38G gene polymorphism with AF in the Chinese population.In the current study, a meta-analysis that includes 856 AF patients and 1015 controls was conducted to determine the relationship of Mink,” “S38G,” “KCNE1,” “atrial fibrillation,” and “polymorphism” were searched in the electronic databases of PubMed, Embase, Web of Science, China Biological Medicine Database, and China National Knowledge Infrastructure. The last updated research date was November 12, 2013, and the publication years ranged from 2002 to 2011.The terms “Mink S38G gene polymorphism and nonvalvular AF, studies on the family history of AF or valvular AF would be excluded; (b) AF was diagnosed as the episodes ≥ 2 occasions (>6 months apart) by serial 12-lead electrocardiography (ECG) or 24 h Holter monitoring. The ECG diagnosis criteria were as follows: (1) P wave disappearance and replacement with irregular baseline fluctuation, with a frequency ranging from 350 per minute to 600 per minute, namely, f wave; (2) extremely irregular ventricular rate; (3) inconsistent QRS complex morphology, the QRS complex becomes broader and changes in the presence of aberrant ventricular conduction and the RR internal remains extremely irregular; (c) the study should be a case-control or cohort study published in an official journal; (d) the study should conform to the Hardy-Weinberg equilibrium (HWE).The selected studies have to be consistent with the following major criteria: (a) assessment of the The data were extracted according to a standard protocol. Three investigators carried out the meta-analysis; two of whom searched for parallel studies, and the third served as the arbitrator in case of discordance between the two investigators. Studies that failed to meet the inclusion criteria, were published repeatedly, or provided insufficient data were excluded. Similar data from different studies were only used once. The abstracted data contained the following: the first author's name, publication year, study region, PubMed identifier number, study design, case selection method, matching factors (if applicable), source population, mean ages of the cases and controls, sample size, variants, major and minor alleles, genotype counts for the cases and controls, HWE among controls, and genotyping methods used. The six selected studies were scored based on the criteria implemented from published recommendations on the evaluation of the quality of genetic association studies .Mink S38G gene polymorphism), recessive (GG versus SG + SS), dominant (GG + SG versus SS), additive (G versus S), homozygous (GG versus SS), and heterozygous genetic models (SG versus SS), were adopted. The relationship of Mink S38G gene polymorphism with AF was compared using odds ratio (OR) and its corresponding 95% confidence interval (CI). The Chi-square-based Q-tests were used to calculate the heterogeneity among the individual studies, with significance level at P < 0.10 [Z-test, with significance level at P < 0.05.In the present meta-analysis, six genetic models, including the allelic , recessive , dominant , additive , homozygous , and heterozygous genetic models  (= 0.016) .Pheterogeneity = 0.057, I2 = 53.5%) and additive genetic models . Metaregression was performed to investigate the heterogeneity source. Heterogeneity under the recessive model can be explained by the SS genotype number of the AF group  and the SG genotype number of the AF group . According to SG1, the whole population was divided into two subgroups. The studies with SG1 < 60 belonged to subgroup  1; the remaining studies with SG1 ≥ 60 belonged to subgroup  2. In the subgroup analysis stratified by SG1, AF risk was only significantly increased in subgroup 2 (P = 0.010) and in subgroup 1, no significant association between Mink S38G and AF was detected (P = 0.073). However, the association strength was much weaker in subgroup 2  and the heterogeneity did not exist in subgroup 2 . By contrast, the heterogeneity was enhanced in subgroup 1  (Tables Heterogeneity was significant under the recessive  Tables .P = 0.004) and SG1 (P = 0.003). The whole population was separated into two subgroups according to SG1, mentioned above. In the subgroup analysis stratified by SG1, AF risk increased significantly in both subgroups. However, the heterogeneity was distinctly reduced in subgroup 2 , but still existed in subgroup 1  . The fail-safe number value was 40 under the additive genetic model which implied that 40 “null” studies should be added to render the general effect insignificant.The funnel plot and Egger's test were used to evaluate the publication bias of the individual studies. A visual publication bias can be detected in the funnel plot . Egger'sT = −3.31, P = 0.080) and the funnel plot was approximately symmetrical , recessive (OR: 1.193), dominant (OR: 1.057), additive (OR: 1.105), homozygous (OR: 1.128), and heterozygous genetic models (OR: 1.078) in the Chinese population. The current results suggested that the individuals with G allele of Mink S38G gene polymorphism may have higher AF susceptibility than the others in the Chinese population.In the present meta-analysis, P = 0.003) and SG1 (P = 0.003) were demonstrated to possibly explain the heterogeneity source. After adjusting SG1, the AF risk only increased significantly in subgroup 2 which was not detected in subgroup 1. Heterogeneity disappeared in subgroup 2, but still existed in subgroup 1, suggesting that SG1 was the primary heterogeneity source. Similarly, under the additive model, SS1 (P = 0.004) and SG1 (P = 0.003) were the heterogeneity sources. In the subgroup analysis adjusted by SG1, the heterogeneity disappeared in subgroup 2 but remained in subgroup 1, indicating that SG1 was the main heterogeneity source.Heterogeneity existed under the recessive, additive, and multiplicative genetic models. Thus, subsequent meta-regression was performed to explore the heterogeneity source. Under the recessive model, confounding factors such as SS1  identified three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 that are associated with AF. Susceptibility loci in 3p22, 5q35, 7q31, 12p12, and 12q24 were also identified by GWAS for PR interval duration. Only one locus around the gene NOS1AP was identified in the QT interval, another cardiovascular trait that is also a good indicator for AF [α and β subunits were encoded by KCNQ1 and Mink genes, respectively [Mink gene mutations can lead to various malignant arrhythmias such as familial long QT syndrome (LQTS) and Jervell syndrome [Mink gene polymorphisms were associated with drug-induced LQTS and nonfamilial arrhythmias [Mink gene mRNA expression increased distinctly in the atrial tissue of the AF patients [Mink gene is important in regulating cardiac rhythm. The possible reasons for the Mink 38G allele associated with AF were as follows. (a) Mink 38G allele could increase Mink gene expression and Iks channel protein synthesis. (b) Mink 38G allele could increase Iks current, thereby shorten the action potential duration, and be predisposed to AF [At present, the gene variation encoding the ion channel was the pathologic factor for familial AF that reduced the Iks . The Iksectively . On the syndrome , 25. Morhythmias . Chevillpatients . Chen etpatients . Thus, ted to AF .Mink S38G gene polymorphism and AF and found that the GG genotype was significantly associated with increased AF risk [Lin et al. 2009) performed a meta-analysis to explore  AF risk . However AF risk , 31. Sec performe AF risk . Compare AF risk . TherefoMink S38G gene polymorphism were still relatively insufficient. The relatively large effect sizes in the current meta-analysis may be attributed to the limited sample size. The Mink expression level was influenced by the Mink S38G gene polymorphism and by other gene polymorphisms, such as KCNQ1 S140G, KCNE2 R27C, and KCNE3 R53H mutations.However, limitations still existed in the present meta-analysis. Large-scale studies on the association of AF with Mink S38G gene polymorphism was significantly associated with AF susceptibility. Patients with the G allele may be predisposed to AF. The current conclusion may guide the formulation of new individual AF diagnosis parameters and therapeutic strategies. Considering the abovementioned limitations, more large-scale studies are needed to confirm the above conclusion.Therefore,


Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN).Cell cycle deregulation is common in human cancer, and alterations of A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk.p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (Ptrend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes .We found that patients with p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.These results suggest that  In the United States, squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 50,000 new cancer cases, causing 11,480 deaths annually . SCCHN hA common feature of human cancer is cell cycle deregulation, and cell cycle progression is governed by the activation cyclin and cyclin-dependent kinases (CDKs), which function together in the G1 phase to initiate S phase and in G2 to initiate mitosis. Through regulation of cyclin-CDK complexes, p27 and p21, two critical CDK inhibitors, act as a fail-safe mechanism involved in DNA repair and apoptosis . Furtherp21and p27 with risk of various cancers, including SCCHN  were digested with the restriction enzymes BsmAI (for p21 C98A) or PstI (for p21C70T)  overnight at 55°C (for BsmAI) or 37°C (for PstI) and separated with 3% Metaphor gel containing ethidium bromide. The genotype of p21 C98A was identified by an A allele with fragment lengths of 77, 92, and 238 bp and a C allele with fragment lengths of 92, 165, and 238 bp. The genotype of p21C70T was identified by a T allele with a fragment length of 298 bp and a C allele with fragment lengths of 173 and 125 bp.We used genomic DNA extracted from the buffy-coat fraction of the blood samples to genotype escribed ,17. We pWe evaluated the genotyping results without knowing the subjects with SPM or without SPM. For quality control purpose, we repeated at least 10% of random samples with a 100% concordance.P values (P < 0.05) and all tests were two-sided. The Chi-squared tests were used to exam differences in distribution of demographic, clinical, and genotyping variables between patients who had SPM and those who did not. Kaplan-Meier methods were used to determine SPM-free survival between different risk groups. Both univariate and multivariable Cox proportional hazards regression models were used for SPM assessment, and details in building the multivariable Cox models were described previously [Statistical significance was determined by eviously . The finSCCHN: Squamous cell carcinoma of the head and neck; SPM: Second primary malignancies; HR: Hazard ratio; CI: Confidence interval; HPV: Human papillomavirus; CDKs: Cyclin-dependent kinases; SNPs: Single nucleotide polymorphisms.The authors declare that they have no competing interests.ZW participated in the design of the study, data analysis, and manuscript writing. EMS participated in study design, statistical analysis and manuscript writing. FZ performed literature review and drafted the manuscript. DL participated in study design and helped to draft the manuscript. ZL carried out the laboratory analysis. LX participated in statistical analysis and helped to draft the manuscript. QW participated in study design, data analysis, and manuscript writing. GL participated in study design, data analysis and manuscript writing. All authors read and approved the final manuscript.


Peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) is involved in the process of tumorigenesis. The two single nucleotide polymorphisms  in the PIN1 promoter region have been suspected of being associated with cancer risk for years, but the conclusion is still inconclusive.Eligible case-control studies were retrieved by searching databases and references of related reviews and studies. Genotype distribution data, adjusted odds ratios (ORs) and 95% confidence (CIs) intervals were extracted to calculate pooled ORs.heterogeneity = 0.012 and GC vs. GG: OR = 0.721, 95% CI: 0.591–0.880; Pheterogeneity = 0.003). Results from genotype distribution data were in agreement with those calculated with adjusted ORs and 95% CIs. No publication bias was detected.A total of 4619 cancer cases and 4661 controls were included in this meta-analysis. Overall, the PIN1 −667T>C polymorphism was not associated with cancer risk, while the −842C allele was significantly associated with reduced cancer risk (CC+GC vs. GG, OR = 0.725, 95% CI: 0.607–0.865; PResults of this meta-analysis suggest that the PIN1 −842G>C polymorphism is associated with decreased cancer risk, but that the −667T>C polymorphism is not. Peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) belongs to the parvulin peptidyl-prolyl isomerase family. With a conserved WW (Trp-Trp) domain, which is responsible for binding to specific sequences of target proteins and recruiting these proteins into signaling complexes Consistent with the critical regulatory role of PIN1 in cancer development, it has been reported that aberrant expression of PIN1 is associated with cancers, such as breast cancer The present meta-analysis was designed to ascertain whether the two common SNPs  of PIN1 are associated with cancer risk and evaluate the impact of ethnicities.Databases of PubMed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched to retrieve eligible case-control studies. Key words of “peptidylprolyl cis/trans isomerase, NIMA-interacting 1”, “single nucleotide polymorphism”, and “cancer” were used and the alternative spellings of these key words were also considered. There was no limitation of search and the last search was performed on March, 2013. Reference lists of related studies and reviews were manually searched for additional studies.Eligible studies were identified according to the following inclusion criteria: (1) case-control studies; (2) investigating the correlation between the −842G>C or −667T>C polymorphism and cancer risk; (3) providing detail genotype frequencies. Studies without detail genotype frequencies were excluded. Searching records were primarily searched by titles and abstracts and then full text articles were retrieved for further evaluation of eligibility. Two reviewers (PJJ and WD) extracted eligible studies independently according to the inclusion criteria. Disagreement between two authors was discussed with another author (ZT) till consensus was achieved.Data of eligible studies was extracted by two authors (PJJ and WD) independently in duplicate with a predesigned data-collection form. The following data was collected: name of first author, year of publication, country where the study was conducted, genotyping methods, ethnicity, cancer type, source of control, number of cases and controls, genotype frequency in cases and controls, adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In this meta-analysis, ethnicity was simply categorized as Asian and Caucasian. Source of control was defined as hospital-based (HB) and population-based (PB) according to the control source. Sample size of studies were defined as large (>500 participants) or small (≤500 participants). In the study by Segat et al To test the distribution of Hardy-Winberg equilibrium (HWE) in controls, chi-square test for goodness of fit was conducted and a p<0.05 indicated disequilibrium of HWE. We assessed the association strength of the PIN1 −667T>C and −842G>C polymorphisms with cancer risk by OR and 95% CIs. The 95% CIs was used for statistical significance test and a 95% CI without 1 indicating a significantly increased or decreased cancer risk. We calculated pooled ORs for homozygote comparison (CC vs. TT or GG), heterozygote comparison (TC vs. TT and GC vs. GG), dominant model (TC+CC vs. TT or GC+CC vs. GG) and recessive (CC vs. GC+GG or TC+TT) model, assuming the dominant and recessive effect of the variant C allele, respectively. We performed subgroup analyses to explore the effects of confounding factors, such as ethnicities, source of control and sample size. By omitting one study each time, sensitivity analyses were performed to investigate individual study' effect on pooled results and test the reliability of meta-analysis results.Chi-square based Q test was utilized to assess the statistical heterogeneity between studies, and heterogeneity was significant when p<0.10. The fixed-effects model (based on Mantel-Haenszel method) and random-effects model (based on DerSimonian-Laird method) were used to calculated the pooled ORs. The fixed-effects model was used when there was no significant heterogeneity; otherwise, the random-effects model was applied Begg's funnel plot and the Egger' linear regression test were conducted to detect publication bias, and a p<0.05 was considered significant After removal of duplicated records, a number of 91 searching records were screened and 8 full-text articles A total of 11 studies were included in this meta-analysis, including 4619 cancer patients and 4661 controls. PIN1 polymorphisms and cancer risk was investigated in 7 kinds of cancer . Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) was used for genotyping in most studies. The detailed characteristics of eligible studies are shown in By pooling data of genotype distribution, in overall comparison, no significant association of the −667T>C polymorphism with cancer risk was found in any comparison model ; Table 2heterogeneity,0.414; To better assess the effect of PIN1 polymorphisms, we calculate pooled OR with adjusted ORs and 95% CIs. Similarly, we found the PIN1 −667T>C polymorphism did not contribute to cancer risk in overall comparison ; Table 3heterogeneity = 0.012 heterogeneity = 0.003; Meta-analysis results from genotype distribution data showed that the −842C allele could significantly reduced cancer risk  was observed after removal of this study.Publication bias were evaluated by Egger's test and Begg's test, and we did not found any evidence of publication bias Click here for additional data file.