DNMT3B) gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra) intron-2 in 32 children (17 boys) with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP . In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group . Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.Primary immune thrombocytopenia (ITP) is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease, both environmental and genetic factors including polymorphisms of TNF-a, IL-10, and IL-4 genes have been suggested to be involved. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP) (C46359T) in DNA methyltransferase 3B ( The affected children are young and previously healthy, and they typically present with a sudden onset of petechiae or purpura 2-3 weeks after a viral infection or immunization. Complete remission occurs in at least 2/3 of cases within 6 months of initial diagnosis , 2. ITP l system . Althougl system –7.FCGR3A and FCGR3B) and tumor necrosis factor-a (TNF-a) and lymphotoxin-a (LTA) genes were found to be associated with chronic childhood ITP. Satoh et al. [βTNF- gene and chronic ITP in adults. In addition, Wu et al. [β exon 5 polymorphism is associated with childhood ITP.Currently, it is generally accepted that both environmental and genetic factors are involved in the pathogenesis of ITP and, especially, interactions between genetic and epigenetic changes. Among the genetic factors, polymorphisms of inflammatory cytokine genes have been related with ITP –10. In ah et al.  observedu et al. , 14 founApart from the polymorphisms of inflammatory cytokine genes, environmentally induced epigenetic changes in gene expression have recently become a new field of research, and a lot of studies investigate the role of these changes in the loss of self-tolerance and the development of autoimmune diseases , 16. EpiDNMT3B) gene promoter and a VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra) intron-2 with an increased risk of ITP in children, in an attempt to elucidate the role of genetic and epigenetic mechanisms in the pathogenesis of such an autoimmune disease.In the present study, we investigated the association of the rs2424913 single-nucleotide polymorphism (SNP) (C46359T) located into DNA methyltransferase 3B  from unrelated families living in Crete, aged 7 months to 14 years, diagnosed with ITP, and hospitalized at the Department of Pediatric Hematology-Oncology of the University Hospital of Crete. The control group consisted of 64 individuals, sex and ethnically matched who had no history of autoimmune or other chronic diseases. The diagnosis of ITP had been made in all children based on history, physical examination, complete blood count, and examination of the peripheral smear, which should exclude other causes of thrombocytopenia. Bone marrow aspiration was performed, when necessary, to rule out other diseases. Ethnic bias within the population studied was minimized by excluding patients that were not of Cretan origin. Parents were informed that cells from the bone marrow would be used for Whole blood was collected in EDTA-containing tubes, and genomic DNA was extracted from the peripheral blood samples using DNA purification kit: Wizard Genomic  according to the manufacturer's instruction. In the study group, the genomic DNA was extracted from bone marrow mononuclear cells (BMMNCs) using the same kit. The extracted DNA was stored at −20°C to be used for the genotyping.DNMT3B (AvrII (Fermentas), which digests the DNA amplified by the T allele into two bands of 207 bp and 173 bp. In contrast, fragments carrying the major C allele lacked the AvrII restriction site. Both undigested and digested PCR products were analyzed through electrophoresis on 2% agarose gel and visualized (with ethidium bromide staining) under ultraviolet (UV) light in reference to a molecular weight marker.The subjects enrolled in this study were genotyped using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) RFLPs method. In brief, the upstream primer 5′-TGCTGTGACAGGCAGAGCAG-3′ and the downstream primer 5′-GGTAGCCGGGAACTCCACGG-3′ were used to generate a region of 380 bp of the promoter of DNMT3B . The ampSimilarly, the upstream 5′-CTCAGCAACACTCCTAT-3′ and the downstream 5′-TCCTGGTCTGCAGGTAA-3′ primers were used to generate the IL-1 Ra region harboring the 86-bp repeats (VNTR). The amplification was performed by using 2,5 U Taq polymerase (Invitrogen). An initial denaturation step at 95°C for 5 min was used, followed by 35 cycles of denaturation (at 95°C for 30 sec), annealing (58°C for 30 sec), and chain extension (72°C for 30 sec), and a final elongation step at 72°C for 5 min. PCR products were directly analyzed by electrophoresis on 2% agarose gel and visualized upon staining with ethidium bromide. Genotypes were scored blindly, and analysis of all ambiguous samples was repeated. Moreover, 10% of the samples were amplified twice for checking the accuracy of the results. Statistical analysis was performed using the GraphPad Prism statistical software method . The distribution of the genotypes and alleles in the group of patients was compared to that of control group using the chi-squared test and Fischer's exact test where necessary, which was also used to determine whether the observed genotype frequencies conformed to Hardy-Weinberg expectations. The level of significance was set to 0.05. The association between polymorphisms and the risk of development of ITP was estimated by odds ratio (OR) and the 95% confidence intervals (CIs).DNMT3B SNP in 32 children with ITP and control group is presented in P = 0.03, OR = 2, 95% CI: 1.06–3.94), thus indicating an apparent association between this allele and ITP in patients of Cretan origin. The distribution of genotype and allele frequencies of rs2424913 IL-1 Ra polymorphism, although we found four different alleles, we focused on alleles I and II and genotypes I/I, I/II, and II/II because of their higher prevalence. The genotype and allelic distribution of IL-1 Ra among children with ITP and the control group is presented in IL-1 Ra between the two groups (P = 0.042). Children with ITP had a significantly higher frequency of genotype I/II, compared to control group . Moreover, genotype I/I as well as allele I was overrepresented in the control group (68.75 versus 50% and 84.43 versus 71.9%), suggesting that allele I may have a decreased risk for development of ITP, whereas the presence of allele II seems to increase 2.12 times the relative risk for disease development .In case of DNMT3B (C46359T) SNP and an IL-1 Ra VNTR polymorphism with susceptibility to ITP.Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized mainly by the destruction of autoantibody-mediated platelets. Despite extensive research efforts during last years, the genetic basis of ITP remains largely unknown. In this study, by performing a case-control association study, we have investigated the possible association of the rs2424913 in vitro and the development of lupus-like syndrome in vivo [DNMT3B promoter polymorphism and the susceptibility to ITP in Chinese population. However, another study reported that DNMT3A and DNMT3B mRNA expressions were significantly lower in ITP patients than in healthy controls, suggesting that aberrant DNA methylation patterns are possibly involved in the pathogenesis of ITP [DNMT3B SNP and the risk of ITP, but no significant differences were found in the genotype distribution between the children with ITP and the controls. However, we found a very low frequency of T/T genotype in our population, whereas in the Chinese population, there was found a distinct prevalence of the T/T genotype and absence of C/C genotype [DNMT3B promoter SNP may be implicated to the pathogenesis of ITP. The DNMT3B C-to-T transition polymorphism (C46359T) examined, in in vitro assays, confers a 30% increase in promoter activity [DNMT3B expression, may result in an aberrant de novo methylation of CpG islands in autoimmunity-mediating genes, thus leading to the development of ITP. However, the role of this gene in ITP seems to be a real “enigma” given that conflicting data have been presented so far. Thus, an aberrant DNA methylation status reflected by increased plasma SAH concentration and decreased expression levels of DNMT3A and 3B has been found in ITP [in vitro. It is also possible that the “T” allele may be in linkage disequilibrium with other susceptibility loci. Altogether, the precise mechanism by which altered DNA methylation patterns induce ITP needs to be studied globally in the view of the concerted action of DNMT3A and DNMT3B, which results in a change of DNA methylation equilibrium in ITP patients.Epigenetic gene regulation has an essential role in determining individual gene function and activity. Epigenetic alterations lead to gene malfunction in a pathological context . DNA met in vivo , 32, 33. in vivo  showed ts of ITP . In the genotype . This fiactivity . Althougphism C469T examinIL-1 Ra polymorphisms may lead to changes in this IL-1 and IL-1 Ra balance and be associated with susceptibility of a variety of autoimmune diseases, such as rheumatoid arthritis, SLE, and ankylosing spondylitis [IL-1 Ra polymorphism in Chinese children with ITP so far [IL-1 Ra polymorphism and the susceptibility of ITP, and we found that IL-1 Ra polymorphism is associated with childhood ITP. The genotype I/II was more frequently detected in children with ITP than in controls. More specifically, we found that the presence of allele II seems to increase 2.12 times the risk for development of ITP, thus assuming that IL-1 Ra polymorphism may be involved in the pathogenesis of ITP. The polymorphism under investigation is caused by the variable copy number of an 86-bp sequence, and the repeat region contains three potential protein-binding sites. Therefore, the variable copy number may have functional significance. Furthermore, allele II has been reported to be associated with more severe clinical outcome in several inflammatory diseases, including systemic lupus erythematosus [As referred above, the pathogenesis of ITP is complicated with cellular immunity and cytokine response playing crucial roles in the pathogenesis , 7. Abnondylitis –43. TherP so far . In the ematosus , rheumatematosus . An incrematosus . The indematosus , 47. ObvA definite advantage of our study, particularly with respect to other association studies, was the attention paid on the selection of a genetically and ethnically homogeneous patient's cohort and control group. As a consequence, the results of this study are unlikely to be biased by sampling. Given that the incidence of pediatric ITP is on the order of 4–6 cases/100,000 population annually, it is extremely difficult to collect easily more patients of Cretan origin. Crete (situated 25°E and 35°N) is the largest island of Greece, with about 0.65 million inhabitants who share the same genetic and cultural background and a common environment. A possible weakness of our study deals with the limited sample size, a fact that is difficult to be overcome easily in a geographically isolated region. DNMT3B SNP as well as the IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP. However, it is in our short-term plans to collect and genotype samples from other geographical areas of Greece despite the substantial differences that may appear in the genetic background of subjects from the mainland Greece . In addition, further studies are needed in order to determine the functional role of the polymorphisms under study, aiming to gain insight regarding the mechanism(s) leading to ITP.In conclusion, our results provide evidence that rs2424913


FTO gene polymorphism and polycystic ovary syndrome (PCOS) susceptibility but revealed mixed results. In this study, we aimed to perform a meta-analysis to clarify this association.Many studies have investigated the relationship between Published literature from PubMed, Embase and CNKI was retrieved. Meta-analysis was performed to calculate pooled odds ratio (OR) with 95% confidence interval (CI) using the random- or fix- effects model.FTO rs9939609 polymorphism (or its proxy) was marginally associated with PCOS risk after adjustment for body mass index (BMI) . However, the marginal association was not stable after sensitivity analysis. In the subgroup analysis by ethnicity, the association was significant in East Asians  but not in Caucasians .A total of 5 studies (4778 cases and 4272 controls) were included in our meta-analysis. The results suggested that FTO rs9939609 polymorphism (or its proxy) might not be associated with risk of PCOS in overall population. However, in East Asians, there might be a direct association between FTO variant and PCOS risk, which is independent of BMI (adiposity).Our present meta-analysis indicated that  Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5–7% of women of childbearing age FTO), located in chromosome 16q12.2 and expressed in the adipose tissue and the brain and muscles, was proved to associate with body mass index and obesity FTO protein regulates energy metabolism to increase the obesity risk The fat mass and obesity associated gene (FTO gene polymorphism and the PCOS susceptibility. Some studies reported that FTO rs9939609 polymorphism (or its proxies) was positively associated with PCOS Up to date, several studies have been performed to investigate the association between FTO gene polymorphism and the risk of PCOS across different ethnic populations.In order to increase the statistical power of individual studies, we performed a meta-analysis to clarify the relationship between FTO gene rs9939069 polymorphism and its association with obesity was first reported in 2007. The search strategy to identify all potential studies involved the use of the following key words: (PCOS OR polycystic ovary syndrome) and (fat mass and obesity associated gene OR FTO). The publication language was restricted to English or Chinese. The reference lists of retrieved articles were hand-searched. If more than one article were published using the same case series, only the study with largest sample size was included.We searched the PubMed, Embase and CNKI databases from 2007 to 2013 since FTO polymorphisms with PCOS; (2) used case-control or cohort design; (3) provided OR with 95%CI or sufficient data for calculation of the estimate. The following information was extracted from each study: (1) name of the first author; (2) year of publication; (3) origin of country; (4) ethnicity; (5) number of cases and controls; (6) mean age and BMI of subjects; (7) OR with 95% CI under an additive model; (8) single nucleotide polymorphisms (SNPs); and (9) P value for Hardy-Weinberg equilibrium (HWE) test in controls. Two authors independently assessed the articles for compliance with the inclusion/exclusion criteria, and resolved discrepancies by group discussion until reaching a consistent decision.A study was included in the meta-analysis only if it met all the following inclusion criteria: (1) evaluated the association of any of the FTO polymorphism with PCOS was estimated by calculating the pooled OR and 95% CI. The significance of the pooled OR was determined by Z test . The Q test was performed to evaluate to the degree of between-study heterogeneity. A random-effects (DerSimonian–Laird) P≤0.10) or absence (P>0.10) of heterogeneity, respectively. Publication bias was assessed by Begg's testP<0.05 was considered statistically significant). To evaluate the stability of the results, we performed a sensitivity analysis by removing one study at a time. Data were analyzed by STATA version 11.0 .The association of The literature search identified a total of 38 potentially relevant articles. Of these, 24 were excluded after reading the title or abstract because of obvious irrelevance, 13 potentially relevant articles remained for further full-text evaluation. Of these, 2 articles 2>0.90), we selected the rs9939609 polymorphism as the representative. Two ethnicities were involved in our 5 studies: 2 studies All included studies used the Rotterdam criteria FTO rs9939609 polymorphism (or its proxies) and PCOS risk under an additive model after adjustment for BMI . Since the study by Li et al. The overall result showed a marginal association between In the subgroup analysis by ethnicity, the association after adjustment for BMI was significant in East Asians  but not in Caucasians .Sensitivity analysis was performed by removing one study at a time. The marginal association after adjustment for BMI was not stable, with ORs and 95%CIs ranging from 1.08 (0.89–1.31) to 1.43 (1.29–1.58).p = 0.462 and Begg's test: p = 0.479).The results suggested no publication bias after adjustment for BMI  was not related to PCOS susceptibility after adjustment for BMI. However, in East Asians, there might be a direct association between FTO variant and PCOS risk since the association was significant after adjustment for BMI. Further studies should be conducted to explore the association of FTO gene polymorphism with PCOS.In conclusions, our meta-analysis results indicated that


P < 0.001 and OR = 0.27; 95% CI = 0.013–0.55, P < 0.001, resp.). No significant difference was found among the groups regarding −1208 A/G polymorphism. In conclusion we found that the IRGM −1161 C/T and −947 C/T polymorphisms but not −1208 A/G polymorphism provide relative protection against PTB in a sample of Iranian population.Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. IRGM1 is an important protein in the innate immune response against intracellular pathogens by regulating autophagy. Polymorphisms in the IRGM genes are known to influence expression levels and may be associated with outcome of infections. This case-control study was done on 150 patients with PTB and 150 healthy subjects to determine whether the IRGM polymorphisms at positions −1208 A/G (rs4958842), −1161 C/T (rs4958843), and −947 C/T (rs4958846) were associated with PTB. The polymorphisms were determined using tetra-amplification refractory mutation system-PCR (T-ARMS-PCR). The results showed that the IRGM −1161 C/T and −947 C/T polymorphisms were associated with decreased susceptibility to PTB (OR = 0.06, 95% CI = 0.03–0.13,  Tuberculosis is a public health problem especially in developing countries and cause of morbidity and mortality throughout the world. According to the World Health Organization (WHO), it is a global emergency  and apprIRGM) induced autophagy in macrophages to control M. tuberculosis [Listeria, Toxoplasma, and Mycobacterium tuberculosis [Mycobacterium tuberculosis is an intracellular pathogen that can persist within host macrophages. It can reside within phagosomes of macrophages and is able to arrest phagosome maturation . Autopharculosis . This prrculosis . There arculosis .The IRGM gene with 5 exons is located on chromosome 5q33.1. The first exon is long and encodes 181 amino acids; the four shorter exons extend more than 50 kb downstream from the first exon , 6.There is little and controversial data concerning the impact of IRGM polymorphisms and susceptibility to PTB. Therefore, the present study aimed to evaluate the possible association between −1208 A/G, −1161 C/T, and −947 C/T IRGM polymorphisms and pulmonary tuberculosis in a sample of Iranian population. This case-control study was performed from December 2010 to January 2012 in the Research Center for Infectious Diseases and Tropical Medicine, the Bou-Ali Hospital, Zahedan, Iran. A total of 150 PTB patients and 150 healthy subjects were enrolled in the study. Ethics committee of the Zahedan University of Medical Sciences approved the project and informed consent was taken from all patients and healthy subjects. All control subjects were from the same geographical origin and were living in the same region as the patients with PTB. The diagnosis of PTB was based on clinical, radiological, sputum acid-fast bacillus (AFB) smear positivity, culture, and response to antituberculosis chemotherapy as described previously , 10. TwoTetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) is a simple and rapid method for detection of single nucleotide polymorphism (SNP) –14. We dμL template DNA (~100 ng/μL), 1 μL of each primer (10 μM), and 15 μL DNase-free water were added. The PCR cycling conditions were 5 min at 95°C followed by 30 cycles of 30 s at 95°C, 30 s at 63°C for −1208 A/G, 65°C for −1161 C/T, 63°C for −947 C/T, respectively, and 30 s at 72°C, with a final step at 72°C for 10 min to allow for complete extension of all PCR fragments. The PCR products were analyzed by electrophoresis on a 2% agarose gel containing 0.5 μg/mL ethidium bromide and visualized by ultraviolet transilluminator. To ensure genotyping quality, we regenotyped all polymorphisms in random samples and found no genotyping mistake.Polymerase chain reaction (PCR) was done using commercially available PCR premix  according to the manufacturer protocol. Into a 0.2 mL PCR tube containing the AccuPower PCR PreMix, 1 For −1208 A/G, the PCR product sizes were 195 bp for A allele, 245 bp for G allele, and 402 bp for two outer primers (control band) . For −11t-test for continuous data and χ2 test for categorical data. A P value less than 0.05 was considered statistically significant. The associations between genotypes of IRGM gene and PTB were estimated by computing the odds ratio (OR) and 95% confidence intervals (95% CI) from logistic regression analyses.The statistical analysis of the data was performed using the SPSS 18.0 software. Demographics and biochemical parameters between the groups were analyses by independent sample P > 0.05). Allele and genotype frequencies of IRGM −1208 A/G, −1161 C/T, and −947 C/T are given in χ2 = 1.19, P = 0.274). A significant difference was observed among case and control groups regarding IRGM −1161 C/T  and −947 C/T . As shown in P < 0.001 and OR = 0.36, 95%  CI = 0.26–0.51, P < 0.001, resp.). The −947 CT genotype was significantly higher in control group (%23.33) than that in PTB (%8.00) and this polymorphism was negatively associated with susceptibility to PTB . The −947 C allele confers a protective role against PTB .For determining of IRGM polymorphisms in PTB patients and comparison of these polymorphisms with healthy individual, a total of 150 pulmonary tuberculosis patients with an average age of 47.5 years  and 150 healthy subjects with a mean age of 44.13 years  were enrolled in the study. There was no significant difference among the groups regarding sex and age  risk in a sample of Iranian population. Our finding revealed the protective role of −1161 C/T and −947 C/T polymorphisms against PTB in our population. No significant difference was found between control and PTB groups regarding IRGM −1208 A/G polymorphism. Mycobacterium tuberculosis. They also reported that the human IRGM plays a role in autophagy and in the reduction of intracellular bacillary load [To the best of our knowledge, there is little information regarding the association of IRGM polymorphisms and tuberculosis and this is the first report from Iran. The earliest report about the role of IRGM in autophagy and defense against intracellular pathogens is attributed to Singh et al. study . They foary load . M. africanum or M. bovis [M. tuberculosis [Intemann et al. for the first time investigated the association between IRGM genotypes and tuberculosis. They found that the IRGM genotype −261 TT provides relative protection against Mycobacterium tuberculosis but not by M. bovis . They prrculosis . Che et rculosis . In contrculosis .A study conducted by King et al. on 370 African American and 177 Caucasian tuberculosis (TB) cases and 180 African American and 110 Caucasian controls showed that single nucleotide polymorphism rs10065172 C/T in IRGM is associated with human vulnerability to TB disease among African Americans [A combination of both innate and adaptive immune responses were involved in the host defense against mycobacterium. Autophagy mediates innate immune responses against mycobacterium by promoting phagolysosomal maturation within macrophages , besidesThe exact reason as to why only a number of the subjects infected with M. tuberculosis develop clinical disease is clearly unknown. There are some evidences recommending that host genetic factors may be important risk factor for development of tuberculosis –20. The In conclusion, our results showed that −1161 C/T and −947 C/T IRGM polymorphisms but not −1208 A/G polymorphism contributes to decreased susceptibility to PTB among an Iranian population. Larger studies with different ethnicitie are required to validate our findings.


To evaluate the association of NOS1 and NOS3 gene polymorphisms with the risk/severity of neonatal respiratory distress syndrome (RDS) among preterm infants.The patient group was 189 preterm infants diagnosed with RDS. The control group was 227 preterm neonates who did not develop RDS. NOS genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique based on LDR.It was found that genotype and allele frequencies of rs2682826 of the NOS1 gene and rs1799983 of the NOS3 gene were not significantly different between the RDS group and the control group. However, when the preterm infants were divided into two and three groups based on gestational age and birth weight, a study of the SNP rs1799983 of the NOS3 gene showed that the GG genotype and G allele frequencies were significantly increased in the RDS groups, the GT genotype and A allele were less frequent among the RDS groups in 26–32.9 weeks of gestational age and in a birth weight subgroup of <1.5 Kg.Our study raises the possibility that a genetic variation of NOS3 could be implicated in the pathophysiology of RDS in the Chinese Han population, especially in very preterm and very low birth weight infants. Nitric oxide (NO) is a modulator of apoptotic and inflammatory cascades and endothelial permeability; it is synthesised by nitric oxide synthase (NOS) from L-arginine. In humans, neuronal NOS (nNOS) encoded by NOS1, inducible NOS (iNOS) encoded by NOS2A, and endothelial NOS (eNOS) encoded by NOS3 are three isoforms of NOS that are expressed in airway epithelium .NOS1 is located on chromosome 12q24.2 and is composed of 29 exons and 28 introns, which encompass more than 160 kb of genomic DNA . The rs2The study of genetic polymorphisms of NOS can help to understand individual variability in their susceptibility to the pathologies of pulmonary disease, especially RDS, which is the most frequent form of respiratory failure in preterm infants. There has been no study that investigated the role of NOS1 polymorphisms in RDS in preterm neonates. The association between the NOS3 gene and NRDS has been investigated in recent studies among Turkish population, but the data remain inconsistent ,9 and thThe Chinese population has over 1,30 billion people, in which the Han population is over 1,17 billion. Due to the variable genetic polymorphisms and distinct geographic residency and environment, predisposition and susceptibility to diseases vary. The aim of the present study is to determine whether the polymorphisms of NOS1 and NOS3 genes in preterm babies were associated with RDS in a Chinese Han population.A total of 416 patients were recruited from Zhujiang Hospital and Guangzhou Woman and Children’s Medical Center from October 2009 to February 2013 for the study. The RDS group was composed of 189 neonates from unrelated families. We defined RDS as the need for supplemental oxygen, a chest radiograph consistent with RDS and the need for continuous positive airway pressure or mechanical ventilation within the first 24 hours of life. The control group was composed of 227 preterm infants without RDS. Exclusion criteria were congenital anomalies, severe infection, and inherited metabolic disorders. Clinical data concerning gestational age, sex, birth weight, and maternal and neonatal clinical histories were obtained from the medical records. The gestational age of the infants were determined based on early ultrasound estimates of gestation and date of LMP. Informed consent was obtained from the parents of the infants, and the study protocol was approved by the local Ethics Committee of Southern Medical University.Genomic DNA was extracted from 2 ml of EDTA-anticoagulated peripheral blood samples, using the QIAamp DNA Kit  according to the manufacturer’s instructions.The SNP genotyping work was performed using an improved multiplex ligation detection reaction (iMLDR) technique, which was newly developed by Genesky Biotechnologies Inc. . This method was based on LDR. In this study, we applied the iMLDR technique on the genotyping of 2 SNP loci in one ligation reaction, which is the rs2682826 polymorphism of the NOS1 gene and the rs1799983 polymorphism of the NOS3 gene. A multiplex of PCR reactions was designed to amplify the 2 SNP loci. The first PCR reaction in 20 μl contained 1x PCR buffer (Takara), 3.0 mM Mg2+, 0.3 mM dNTP, 1 U of Hot-Start Taq DNA polymerase (Takara),1 μl of primer mixture 1 and ~20 ng of genomic DNA. The second PCR reaction in a 20 μl volume contained 1× GC Buffer I (Takara), 3.0 mM Mg2+, 0.3 mM dNTP, 1 U of Hot-Start Taq DNA polymerase (Takara),1 μl of primer mixture 2 and ~20 ng of genomic DNA. The primer information in two mixtures is described as follows.rs1799983F:CAATGAGGGACCCTGGAGATGA,rs1799983R:CCCAGTCAATCCCTTTGGTGCT;rs2682826F:CAGGGGAACCCCAGAGAAAAAA;rs2682826R:GCCTCCTGTCCTTGTCGCTGT.The PCR program for both reactions was 95°C 2 min; 11 cycles × ; 24 cycles × ; and 72°C 2 min; hold at 4°C. The two PCR products were equally mixed and purified by 1 U of shrimp alkaline phosphatase’s digestion at 37°C for 1 hr and at 75°C for 15 min. The ligation reaction in 20 μl contains 1 × ligation buffer, 80 U of Taq DNA Ligase (NEB), 1 μl of labeling oligo mixture, 2 μl of probe mixture and 5 μl of purified PCR product mixture. The oligo or probe information in these two mixtures is described as follows:rs1799983FG:TTCCGCGTTCGGACTGATATTGCTGCAGGCCCCAGATCAG,rs1799983FP:CCCCCAGAACTCTTCCTTCTGCTTTTTTTTTTT,rs1799983FT:TACGGTTATTCGGGCTCCTGTTGCTGCAGGCCCCAGATCAT;rs2682826RA:TACGGTTATTCGGGCTCCTGTTGCCGACAAGGGCAACTGAT,rs2682826RG:TTCCGCGTTCGGACTGATATTGCCGACAAGGGCAACTGAC,rs2682826RP:GGGTGCATGAAACCACTGGATTTTTTTTTT.The ligation cycling program was 95°C 2 min; 38 cycles × ; hold at 4°C. A 0.5 μl of ligation product was loaded in ABI 3730 × l, and the raw data were analysed by GeneMapper 4.1. All of the primers, probes and labeling oligos were designed by and ordered from Genesky Biotechnologies Inc. .Statistical analysis was performed using the SPSS package program . Data were expressed as the mean ± SD or percentage. Allelic frequencies were calculated by the gene-counting method. A statistical comparison of two groups was performed by an unpaired Student’s t-test, while APGAR scores were compared with the Mann–Whitney U-test. A chi-square test was used to test the expected type frequencies, assuming Hardy-Weinberg equilibrium. The chi-square test or Fisher’s exact test was used for calculation of the significance of differences in genotype and allele frequencies. P < 0.05 was considered to be statistically significant.The RDS group was composed of 189 preterm infants, and eight of the 189 infants (4.2%) died in the follow-up period due to RDS. The control group was composed of 227 preterm infants without RDS and five (2.2%) died for other diseases. All of the infants come from the Han population in south China. The genotypes in the population were in Hardy-Weinberg equilibrium . The demographic characteristics of the RDS and control groups are summarised in Table As shown in Tables For the NOS3-1799983 SNP loci, in the 26–32.9 weeks of gestational age subgroup, GG and GT genotype frequencies were 41.3% and 56.3% of the control group and 65.8% and 30.8% of the RDS group, respectively (P = 0.001), there were marked increases in the G allele frequencies in the RDS groups in this gestational age group (P < 0.05). In the 33–36.9 weeks of gestational age subgroup, the difference in genotype distributions and allele frequencies did not reach statistical significance (p > 0.05)  and rs1799983 combined genotype (GT + TT), and we observed that the frequencies of the rs1799983 polymorphism did not markedly influence the complications, duration of oxygen therapy, mechanical ventilation (including CPAP) and hospitalisation. There were also no statistically significant differences between the demographic characteristics of the two groups except for gestational age, birth weight and use of antenatal steroid between the genotypes Table .RDS is a multifactorial disease, and several genetic factors could interact with environmental factors in determining the risk of the disease. Both the incidence and severity of RDS have decreased markedly since the introduction of antenatal steroids and pulmonary surfactant replacement therapy, yet the incidence of complications remains a cause of concern . SeveralNitric oxide mediates multiple physiological functions, including neurotransmission, immunoregulation, angiogenesis, antiplatelet activity, and surfactant maturation or secretion. Given the many physiological roles for NO and its rapid reaction and inactivation in cellular systems, strict control of NO production is crucial for its selective actions. NO is critical for the maturation of pulmonary structure and function. Research in animals has suggested that NOS3 gene-deficient mice suffered defective lung vascular development and fatal respiratory distress .Several polymorphic variations of the NOS3 gene are now known and have been investigated with respect to disease risk. A few literature reports have revealed that the NOS3 gene Glu298Asp (rs1799983) polymorphism is associated with an increased incidence of cardiovascular disorders and cerebrovascular diseases . GodfreyThis study is the first to examine the impact of the NOS1 gene polymorphism on the risk and severity of RDS in preterm infants; we found no significant difference in the genotype or allele frequencies between the control and the RDS infants. Similarly, the difference in the genotype distributions of the NOS3 gene between the two groups did not reach statistical significance. However, when the preterm infants were divided into two groups by gestational age and three groups by birth weight, we found that, for the NOS3 gene, the GG genotype and G allele increased while the GT genotype and T allele decreased, and infants with the GG genotype and G allele of NOS3 were less likely to have development of RDS in the 26–32.9 weeks of gestational age subgroup and the birth weight <1.5 Kg subgroup.Two meta-analyses showed that inhaled nitric oxide could alleviate persistent pulmonary hypertension in the neonates, but for the treatment of respiratory failure in preterm infants, routine use of inhaled nitric oxide cannot be recommended ,23. It iA limitation of our study is that our sample size was not large enough to compare the control and RDS groups, which could lead to false-negative results in association studies. The sample was not large enough to explore gene by gene interactions, it is possible that having more than one susceptibility gene could result in different respiratory outcomes. Furthermore, only two polymorphisms that are potentially involved in RDS pathogenesis have been considered in this paper; thus, the roles of other SNPs in NOS genes or in other different genes cannot be excluded.In conclusion, our data suggest the lack of an association between the rs2682826 polymorphism of the NOS1 gene and the development of RDS in a Chinese Han population. We observed that there is a gestational age and birth weight -related association between the rs1799983 polymorphism of the NOS3 gene and the development of RDS in this population. However, further investigations of NOS3 genetic variations in combination with other relevant genes  will most likely provide more mechanistic insight into RDS processes. Additional identification of how NOS3 genetic variation is translated to altered enzyme and/or cellular function will also be informative. This pilot study could offer data on which further studies can be planned. Very large-scale studies of genetic, environmental and obstetric factors will be needed before effective preventative strategies can be devised.RDS: Respiratory distress syndrome; NOS: Nitric oxide synthase; iMLDR: Improved multiplex ligation detection reaction; FeNO: Fractional exhaled nitric oxide; SNP: Single nucleotide polymorphism.The authors declare that they have no competing interests.WS carried out the molecular genetic studies, participated in the sequence alignment and drafted the manuscript. JD participated in the sequence alignment. BW participated in the design of the study and performed the statistical analysis. QZ conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.


Some studies have shown that endoscopist specialty is associated with colorectal cancers missed by colonoscopy. We sought to examine the relationship between endoscopist specialty and polypectomy rate, a colonoscopy quality indicator. Polypectomy rate is defined as the proportion of colonoscopies that result in the removal of one or more polyps.A cross-sectional study was conducted of endoscopists and their patients from 7 Montreal and 2 Calgary endoscopy clinics. Eligible patients were aged 50–75 and covered by provincial health insurance. A patient questionnaire assessed family history of colorectal cancer, history of large bowel conditions and symptoms, and previous colonoscopy. The outcome, polypectomy status, was obtained from provincial health administrative databases. For each city, Bayesian hierarchical logistic regression was used to estimate the odds ratio for polypectomy comparing surgeons to gastroenterologists. Model covariates included patient age, sex, family history of colorectal cancer, colonoscopy indication, and previous colonoscopy.In total, 2,113 and 538 colonoscopies were included from Montreal and Calgary, respectively. Colonoscopies were performed by 38 gastroenterologists and 6 surgeons in Montreal, and by 31 gastroenterologists and 5 surgeons in Calgary. The adjusted odds ratios comparing surgeons to gastroenterologists were 0.48 (95% CI: 0.32–0.71) in Montreal and 0.73 (95% CI: 0.43–1.21) in Calgary.An association between endoscopist specialty and polypectomy was observed in both cities after adjusting for patient-level covariates. Results from Montreal suggest that surgeons are half as likely as gastroenterologists to remove polyps, while those from Calgary were associated with a wide, non-significant Bayesian credible interval. However, residual confounding from patient-level variables is possible, and further investigation is required. Colorectal cancer (CRC) screening programs are either in preparation or ongoing in all Canadian provinces and many developed countries . ColonosOf the many quality indicators identified, only ADR has been shown to independently predict CRC diagnosis after colonoscopy, an important public health outcome that suggests failure of screening . HoweverSome studies have shown endoscopist specialty to be associated with cancers missed by colonoscopy -18, raisThe objectives of the present study were to determine whether there is a difference in polypectomy rates between surgeons and gastroenterologists beyond what is attributable to differences in patient risk profiles, and to assess the variability in polypectomy rates within each specialty.We conducted a cross-sectional analysis combining data from 2 prospective cohort studies. Recruitment for the first cohort occurred between January and March 2007 in Montreal and Calgary for the purpose of developing an administrative data algorithm to identify screening colonoscopies. The second cohort was recruited between January 2008 and March 2009 in Montreal to provide additional subjects for the purpose of the present study. Seven hospitals participated in Montreal: Royal Victoria Hospital, Montreal General Hospital, St. Mary’s Hospital Centre, Jewish General Hospital, Hôpital Maisonneuve-Rosemont, Hôpital Fleury, and Centre hospitalier de l’Université de Montréal. Two institutions participated in Calgary: Foothills Medical Centre and Peter Lougheed Centre. The same data collection methods were used for both cohorts and at all sites. Ethics approval was obtained from the McGill University Faculty of Medicine Institutional Review Board and the research ethics boards at each study site.Participating physicians were staff endoscopists at the study hospitals with provincial health insurance billing privileges for colonoscopy. A research assistant approached consecutive patients who were waiting for their colonoscopy with a study physician in the endoscopy waiting room on select days. Eligible patients were aged 50–75 and covered by provincial health insurance. Reasons for not being covered by provincial health insurance include being in the military or RCMP, being a treaty status Indian, and being a resident of another province. The reason for this exclusion criterion is that we were only able to link to provincial records in Quebec and Calgary.The research assistant explained the study, obtained consent, and administered a brief questionnaire to patients on socio-demographics, history of gastrointestinal conditions, large bowel symptoms, previous CRC screening tests, and family history of CRC.Data on polypectomy status were obtained from physician billing records from the Régie de l’Assurance Maladie du Québec (RAMQ) and Alberta Health and Wellness (AHW). The Alberta ambulatory care database also provided polypectomy status for Albertan patients. For patients who underwent more than one colonoscopy during the study period, we included only the first visit in the analyses.Bayesian hierarchical logistic regression models were fitted to estimate the association between endoscopist specialty and polypectomy rate. This technique accounts for endoscopist-level clustering, and allowed us to estimate the odds ratio at the endoscopist level, while adjusting for patient-level risk factors for CRC and adenoma, including: age (50-54/55-59/60-64/65-70/70-75), sex, family history of CRC (y/n), previous colonoscopy (y/n), and colonoscopy indication (screening/non-screening). Screening was defined as no history of large bowel symptoms  in the past 6 months, and no history of gastrointestinal conditions . To estimate the variability of polypectomy rates within each specialty, endoscopist-specific rates were computed from random intercepts for endoscopists. Covariates were centered around their respective means, so that the inverse logits of the intercepts yielded endoscopist-specific rates for typical patients. All analyses were conducted using WinBUGS software version 1.4.3 . Diffuse or wide prior distributions were used for all parameters in all models. Ninety-five percent credible intervals, the Bayesian equivalents of the frequentist confidence intervals, are indicated by CrI.We took measures to account for the imperfect accuracy of health administrative data. For Quebec, we adjusted polypectomy rates using previously estimated sensitivity, 84.7% (95% CI: 79–89%), and specificity, 99.0% (95% CI: 98–100%), of the RAMQ polypectomy billing code . The adjIn Montreal, 2,134 (81.6%) of the 2,614 patients approached were eligible and consented to participate. A total of 38 gastroenterologists, 6 surgeons, and 1 internist performed 1,906 (89.3%), 207 (9.7%), and 21 (1%) colonoscopies, respectively. The patients seen by the internist were excluded from further analysis, as the sample size was too small to make inferences about this specialty. Hence 44 endoscopists and 2,113 patients from Montreal were included. The average number of patients per endoscopist was 48, ranging from 4 to 154 among gastroenterologists, and 9 to 86 among surgeons.In Calgary, 541 (88.1%) of the 614 patients approached were eligible and consented to participate. A total of 31 gastroenterologists and 5 colorectal surgeons performed 444 (82.1%) and 94 (17.4%) colonoscopies, respectively. Three (0.6%) patients were excluded from analysis because their colonoscopies were performed by trainees. The final sample for Calgary included 37 endoscopists and 538 patients. The average number of patients per endoscopist was 15, and ranged from 1 to 73 among gastroenterologists, and from 6 to 30 among surgeons. Table The hierarchical logistic regression results with polypectomy as the outcome for Montreal and Calgary are shown in Table To illustrate variability of polypectomy rates, endoscopist-specific polypectomy rate estimates from hierarchical logistic regression for each specialty are shown in Figure Using a combination of primary and health administrative data from Montreal and Calgary, we estimated the association between endoscopist specialty and polypectomy rate. We found a clinically important difference between endoscopist specialities in Montreal, with surgeons being approximately 50% less likely than gastroenterologists to remove polyps. A similar trend was observed in Calgary but wide credible intervals preclude a definitive conclusion. Patient risk factors yielded odds ratios consistent with the literature, including increase in the probability of polypectomy with increasing age. However, despite statistical adjustment, residual confounding due to patient-level risk factors may contribute the observed difference between specialties.Several prior studies have examined the association between endoscopist speciality and missed CRCs. In a retrospective cohort study using population level data from Ontario, Bressler et al. identified endoscopist specialty as a risk factor for incident CRCs post-colonoscopy among both male and female patients . In contWe determined the variability in polypectomy rates within each specialty, and found considerable variation in both specialties. Several studies have reported important variation in ADRs by specialty. Barclay et al. examined 2,053 screening colonoscopies by 12 endoscopists and found that ADRs varied from 9.4 to 32.7% . Chen etOur results suggest a clinically important difference in polypectomy rates between surgeons and gastroenterologists after adjusting for patient-level factors, as well as substantial variation among all endoscopists. Some of this variation may be explained by endoscopist-level factors such as training, practice factors, and technical factors. Recently, performance quality was compared in trainees with similar endoscopy experience; gastroenterology trainees outperformed surgery trainees on several quality indicators including colonoscopy completion rate, polypectomy rate, ADR, and withdrawal time . One CalPractice factors such as setting and annual case volume may also contribute to variation among endoscopists. For example, Bressler et al. and Baxter et al. both found non-hospital based colonoscopies to be associated with increased risk of missed cancers ,16. A reIn terms of technical factors, withdrawal time has been identified as a significant predictor of ADR in some studies. Results from the Bowel Cancer Screening Programme in England show a significant increase in ADR among endoscopist with mean withdrawal time of 11 minutes or longer compared to those with mean withdrawal time of less than 7 minutes . InvestiA major strength of our study is primary data collection on patient level CRC risk factors that enabled adjustment for colonoscopy indication, family history of CRC and previous colonoscopy. This is important because polypectomy rate is a function of both patient risk and endoscopist performance.One study limitation is residual confounding. Although we adjusted for many important patient risk factors, it is possible that differences in the characteristics of patients referred to surgeons and gastroenterologists were not adequately captured by the patient-level covariates. A second limitation is potential misclassification, as data on polypectomy status were derived from provincial health administrative databases. To address this issue, we employed methods to adjust for the imperfect accuracy of health administrative data in both provinces. Using health administrative data whilst acknowledging and accounting for its limitations is good practice in clinical and health services research. However, our approach to misclassification adjustment for the Montreal data may have introduced bias if misclassification was differential between surgeons and gastroenterologists. Differences in administrative data quality between specialties may arise from differences in billing practices. Nevertheless, it is reassuring that the Calgary sample, where misclassification was reduced by combining two data sources, showed results in the same direction as the Montreal sample. Thirdly, hierarchical modeling was used to estimate the rates as it has the advantage of conservatively bringing unstable estimates closer to the overall mean so that they are less likely to affect the range of variation in polypectomy rates . While uAlthough our findings highlight the important issue of the discrepancy in quality between surgeons and gastroenterologists, the lack of endoscopist-level variables in our study preclude us from isolating the modifiable predictors of endoscopist performance. Future studies aimed at teasing out such factors would help inform changes to training, accreditation, and quality assurance programs. We hope that our findings will serve as impetus for such investigations.In conclusion, we found that surgeons were less likely to remove polyps compared to gastroenterologists, and that considerable variation in polypectomy rates exists within each specialty. Using polypectomy rate as an indicator of colonoscopy quality, our findings showed a difference in practice quality between the two specialties despite controlling for variations in patient risk profiles. Potential reasons for this discrepancy, such as training, practice volume, and technical factors, need to be investigated in future studies. Our findings suggest that the difference in ADRs may begin at the level of polyp removal, and lend further support for the use of polypectomy rate as a colonoscopy quality indicator.The authors declare that they have no competing interests.MJ conducted the data analysis and drafted the manuscript. MJS conceived of the study, participated in its design, and helped draft the manuscript. ANB participated in the study design and contributed to the data collection. LJ participated in the study design and advised the analysis. RJH contributed to study data collection. All authors contributed to the interpretation of the findings, and read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/13/78/prepub


Thermic effect of a meal (TEF) has previously been suggested to influence appetite.The aim of this study was to assess whether there is an association between appetite and TEF. Second, to examine whether protein intake is associated with TEF or appetite.r-value with 95% confidence interval (95% CI). The I2 value quantifies the proportion (%) of the variation in point estimates due to among-study differences.Individual participant data (IPD) meta-analysis on studies were performed at the Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. Five randomized meal-test studies, with 111 participants, were included. The included studies measured energy expenditure (EE) in respiration chambers and pre- and postprandial appetite sensations using Visual Analog Scales (VAS). The primary meta-analysis was based on a generic-inverse variance random-effects model, pooling individual study Spearman's correlation coefficients, resulting in a combined iAUC) . Similarly, Composite Appetite Score (CAS) was not associated with TEFiAUC . Posthoc analyses showed no association between satiety or CAS and TEF expressed as a percentage of energy intake (EI) (P>0.49) or TEF expressed as a percentage of baseline EE (P>0.17). When adjusting for covariates, TEFiAUC was associated with protein intake (P=0.0085).The IPD meta-analysis found no association between satiety and TEF expressed as the incremental area under the curve . Human appetite involves repeated increases and decreases in the desire to eat and is controlled by psychological, physiological, and biochemical mechanisms , 2. TherTEF has previously been suggested as one of the mechanisms that influences appetite sensations, including satiety , 6. StroStudies on appetite and thermogenesis have shown protein to be superior to other macronutrients in promoting satiety , 7. In aEven a small positive association between TEF and satiety could have clinical implications during weight loss. We therefore undertook an individual participant data (IPD) meta-analysis on studies previously conducted at our department, to investigate whether an association between the perception of appetite and TEF exists, and whether protein intake is an influential factor.Studies conducted at the Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark, from 1992 to 2006 were available for inclusion in this study. Studies were included if they contained: 1) data on at least 24-h EE measurements in whole-body respiration chambers; 2) baseline measurements and a minimum of three measurements of appetite sensations after a dinner meal using visual analog scales (VAS); and 3) detailed descriptions of energy intake (EI). To obtain individual energy balance during the chamber stay, EI provided was based on equations estimating EE. In studies where active components  were tested, only the control measurements done without these active components were included in this IPD meta-analysis. If more than one measurement was carried out on the same participant, and if both measurements matched the criteria above, only the last measurement was included. Finally, all included participants had to be healthy, non-smoking, and non-elite athletes (less than 10 h of exercise a week).3 open-circuit respiration chamber at the Faculty of Science . The design of the chambers has been described in detail elsewhere  with the most positive and most negative sensations at opposite ends of the line. Participants mark the line at a point corresponding to their perceived appetite at a given time. For satiety, the question was ‘How satisfied do you feel?’, and the text anchors were ‘I am completely empty’ and ‘I cannot eat another bite’. For fullness, hunger and prospective food intake the questions were ‘How full do you feel?’ , ‘How hungry do you feel?’  and ‘How much do you think you could eat?’ , respectively.The reproducibility and validity of VAS have previously been examined by Flint et al. , who conData were acquired by contacting the principal investigators, searching old records, and contacting the research department where the studies were conducted. The data of all of the included participants were checked for duplicates and were checked twice (by a second reviewer) before being included in the IPD meta-analysis. Data were extracted from previously collected data and were treated as confidential.iAUC and CAS.Data on appetite  just before ingestion of the dinner meal and until 180 min after the meal were extracted from each of the included studies. Similarly, data on EE measurements 30 min before the dinner and until 180 min postprandially were also extracted. Furthermore, data on sex, age, height, body weight, EI, fat-free mass, fat mass, body fat percentage, and tea/coffee ingested after dinner (yes/no) were also collected. VAS was calculated as the incremental area under or over the curve  using VAS measurements filled out immediately before the dinner as baseline. The examined appetite measures were SatietyiAUC) and expressed in kJ/3 h. For the purpose of sensitivity analysis, we also scrutinized other ways to interpret TEF: (EI); and ; and  TEF as tAll included studies were randomized controlled trials with either parallel –16 or crr-coefficient and the corresponding standard error (SE), reflecting the level of statistical significance in the individual tests for association in the different eligible trials. The SE for the non-parametric Spearman's r-coefficient (SE[r]) was estimated from the (two-sided) P-value converted into a standard normal score (Z), which enabled an estimate of SE[r] using Wald-test methodology (Z[r]= r/SE[r]). All results are reported with 95% confidence intervals (95% CI), that were calculated as the estimate for coefficient r±1.96*SE. For the purpose of sensitivity analysis, these Wald-test-converted SEs were re-confirmed when estimated using the approach proposed by Thompson et al. . These hierarchical models derived from maximum likelihood estimates were performed using the SAS software (version 9.2).We performed a number of pre-specified sensitivity analyses based on a statistically more advanced hierarchical model. At level one in the hierarchical model, participants were compared with others from the same study , enabling the entire dataset to be analyzed as if it originated from a single study . A randoad libitum dinner meal . Pooling the data from these five individual trials produced a combined Spearman's r-coefficient of 0.06 (95% CI: −0.16 to 0.28), providing no support to the hypothesis of an association between satiety and TEF (P=0.58). This result was based on a small amount of heterogeneity, with a negligible degree of inconsistency (I2= 15.8%). For sensitivity, we compare this with the more naïve approach – combining all participant data into one correlation analysis (i.e. ignoring the study structure), also resulting in an overall statistically non-significant Spearman's r-coefficient . Inclusion of covariates did not affect the association between satiety and TEFiAUC (see Supplementary file).As illustrated in iAUC (P=0.45); the pooled Spearman's r-coefficient from these five trials was r=0.08 (95% CI: −0.12 to 0.28). As presented in r-values ranged from −0.20 to +0.31, all being statistically non-significant (P>0.20), and apparently with no inconsistency (I2=0%). For sensitivity, combining all participant data into one correlation analysis also resulted in an overall statistically non-significant Spearman's r-coefficient . Inclusion of covariates did not affect the association between CAS and TEFiAUC (see Supplementary file).There was also no association between CAS and TEFiAUC; middle being in relation to satiety; lower in relation to CAS.iAUC and protein intake was found (P=0.57), with the pooled Spearman's r-coefficient being 0.08 (95% CI: −0.20 to 0.36); with a moderate inconsistency across studies (I2=47.8%). Combining all participant data into one correlation analysis  also resulted in an overall statistically non-significant Spearman's r-coefficient . However, we note that one study . An association between TEFiAUC and protein intake was observed (P=0.009) when including the covariates: Sex (P=0.01), caffeine intake (P<0.05), and EI in the dinner meal (P=0.02) (see Supplementary file).No association between TEFne study  showed aP=0.75), as the pooled analysis showed a combined Spearman's r-coefficient of −0.03 (95% CI: −0.24 to 0.17); with a low degree of inconsistency (I2=5.8%). The individual study results ranged from −0.24 to +0.38 with no indication of statistically significant results (P>0.15). Inclusion of covariates did not affect the association between satiety and protein intake (see Supplementary file).Relating the satiety with protein intake did not indicate any association . Pooling the data from these five individual trials produced a combined Spearman's r-coefficient of −0.06 (95% CI: −0.26 to 0.14), providing no support to the hypothesis of an association between CAS and TEF (P=0.57). Inclusion of covariates did not affect the association between CAS and protein intake (see Supplementary file).Finally, for CAS in relation to the protein intake, the Spearman's EI and satiety with all participant data combined resulted in an overall non-significant Spearman's r-coefficient . Similarly, correlation analysis between TEF% and CAS also produced a non-significant Spearman's r-coefficient .Posthoc correlation analysis between TEF%r-coefficient . Finally, similar analysis between TEF% and CAS showed a non-significant Spearman's r-coefficient .Posthoc correlation analysis between TEF% and satiety including participant data from all included studies resulted in a non-significant Spearman's iAUC and the appetite measures, satiety, and CAS. Similarly, no associations were seen between TEF%EI or TEF% and the appetite measures.We found no association between TEFEI). Another study by Westerterp-Plantenga et al. , fat, carbohydrate, and alcohol were ingested . NeverthP=0.57). However, including potentially confounding factors in the model resulted in an overall statistically significant Spearman's r-coefficient (P=0.009). This association between protein and TEF is supported by existing evidence. The reported TEF for protein is 20–30% of energy content compared to fat (0–3%) and carbohydrates (5–10%)  , 51.2. One hundred of the 111 included subjects were in weight-stable conditions with study specific mean weight changes of no more than −0.2 kg±1.2 kg to 1.2 kg±3.9 over 28 days to 6 months. Only 11 of the included subjects had a weight loss of no more than 13.1±0.6 kg over 8 weeks prior to the measurements in the respiration chambers  but no difference between the quartiles was found for body fat (P=0.18). Whether obesity affects the association between satiety and TEF is also uncertain. This could possibly complicate the comparison of the present study with studies performed on normal-weight participants with a BMI < 25 kg/m2.The participants in the present study had an average BMI of 30 kg/mchambers , 52. Numchambers –55. Howechambers –58. A poP>0.48) in the present study makes it unlikely that a longer measurement period would alter these findings significantly . The calculation method for TEF did not influence these findings. However, even though our study did not show any associations, this does not rule out the possibility that associations may be present at higher protein intakes.


All participants were non-Hispanic white women. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele ; the OR was 1.09  after excluding data from the center (Hawaii) that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ≤50 years versus older women  that remained statistically significant after excluding Hawaii data . No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women.The association of ovarian carcinoma risk with the polymorphism rs1271572 in the  Previously, the multiethnic Hawaiian Ovarian Cancer Study evaluated four single nucleotide polymorphisms (SNPs) in the ESR2 gene, as well as their associated haplotypes, in relation to risk of borderline and invasive ovarian cancer and found that rs1271572 in the promoter region of the gene may be an ovarian carcinoma susceptibility marker TT) carriers had a 79% increase in risk (95% CI: 1.15–2.79) compared to women with the GG genotype. White women had more than a two-fold increase in risk . In the present study, we performed a replication analysis of our putative significant findings by genotyping rs1271572 among participants in nine additional studies within the Ovarian Cancer Association Consortium (OCAC), a forum for researchers to evaluate promising genetic associations with ovarian cancer with increased power The human ERβ gene  and controls  was similar . Minor aTT genotype had increased ovarian carcinoma risk  compared to carriers of any G allele (recessive genetic model)  . This ORc model) . ExcludiTT genotype had a 35% increased risk of ovarian carcinoma  compared to G allele carriers. No genetic associations were observed among women >50 years old . The association of the TT genotype with risk among women ≤50 years old was also statistically significant in two individual studies, BAV  and MAL  and in the pooled analysis when HAW data were excluded . The association of the TT genotype with risk was also higher in premenopausal  compared to postmenopausal women , although the test for heterogeneity in effect was not significant (p = 0.82). No heterogeneity of the associations was observed among studies for any of the models (p range: 0.13–0.84). No effect modification by gravidity, parity, menopausal status, and use of contraceptive and menopausal hormones was found for the association of rs1271572 with risk (data not shown). No heterogeneity of effects was observed by tumor histology (p range: 0.20–0.87) (There was a significant interaction between genotype and age (p = 0.02) . Among y20–0.87)  or stageTT genotype with ovarian carcinoma risk, particularly among younger women ≤50 years of age. This significant association of rs1271572 with the risk of ovarian cancer among younger women might result from the higher concentrations of circulating estrogens among pre- and perimenopausal women. By analogy, we hypothesize that among postmenopausal women with lower estrogen levels, ESR2 functional variation would not be an important contributor to risk.In this pooled analysis of ten case-control studies, we found a modest association of the rs1271572 ESR2 gene, near (−53 bp upstream) the AP-4/MyoD binding site ESR2 responsiveness to transcription regulators.A potential causal association of rs1271572 with the risk of ovarian cancer is supported by the finding that it maps to the promoter of the Although the specific role of ERβ in carcinogenesis is not known, there is convincing evidence that ERβ inhibits proliferation and motility of ovarian cancer cells and plays an important role in apoptosis ESR2 variation in relation to ovarian cancer risk, using a haplotype approach. No statistically significant associations were found, although one haplotype was associated with an increased risk of invasive clear cell carcinoma. While the rs1271572 SNP was not genotyped in this study, it was in the haplotype block represented by the rs1271530 SNP which is in a strong linkage disequilibrium (r2 = 0.9) with rs1271572 based on the HapMAP data among whites. A previous genome-wide association study (GWAS) Previously, Pierce et al. evaluated The strengths of this investigation are the population-based nature of the studies included and the stringent genotyping quality control procedures established by the OCAC. A further strength is the large sample size and the relatively high allele frequency. The False Positive Report Probability ESR2 gene may influence the risk of invasive ovarian carcinoma, especially among younger women.In conclusion, the results of this pooled analysis suggest that the rs1271572 SNP in the All studies were approved by the review boards and ethics committees of their parent institutions, and written informed consent was obtained from all participants. In addition, Duke University has Institutional Review Board approval as a data coordinating center. All data were analyzed anonymously.This pooled analysis of nine population-based studies from Australia [the Australian Ovarian Cancer study and the Australian Cancer Study: Ovarian Cancer (AUS)], the United States , and Europe  and one hospital-based study [Bavaria Case-Control Study (BAV)] included 4946 cases with primary histologically-confirmed invasive ovarian carcinoma and 6582 controls. Control subjects were randomly selected from the same geographical areas as cases. Eligibility criteria for controls included age 18 years or older, no prior history of ovarian cancer, and having at least one intact ovary. All cases and controls were non-Hispanic white women. A detailed description of the studies has been previously published and is summarized in Genotyping for the AUS study was performed using the Sequenom iPlex gold genotyping platform . All other studies used TaqMan allelic discrimination assay . We used the following quality control criteria that were established by the OCAC to measure the acceptability of the genotyping results: (1) >3% sample duplicates included, (2) concordance rate for duplicate samples ≥98%, (3) overall call rate (by study) >95% and (4) call rate >90% for each 384-well plate (5) no more than 5% difference in call rates between cases and controls, and (6) cases and controls intermixed on each plate. In addition, consistency across laboratories was confirmed by genotyping a common set of 95 DNAs  with the requirement of >98% concordance in genotype calls. All ten studies met each of the criteria. Genotyping quality was also assessed using tests for Hardy-Weinberg equilibrium (HWE). The genotype distribution for the SNP among controls was consistent with HWE in all but one study . Exclusion of this study did not appreciably affect the reported results.Gene and allele nomenclature was according to the National Center of Biotechnology Information.T allele carriers, using women with the GG genotype as the reference group. We also performed genetic analyses testing a log-additive model in which genotype was categorized by three levels  representing number of variant alleles. In addition, we compared risk among women with the TT/GT versus GG genotypes (testing a dominant genetic model) and among women with the TT genotype versus the GG/GT genotypes (testing a recessive genetic model). Based on the Akaike Information Criterion (AIC), the recessive model provided the best fit for the data. All models are presented in tables for comprehensiveness .Statistical analyses were performed using the SAS statistical package . The chi-square test for association was used to compare the allele frequency distributions among controls across studies, and the chi-square test for goodness-of-fit was used to test consistency with the HWE for each study and overall. The association of the rs1271572 polymorphism with ovarian carcinoma risk was assessed using multivariate logistic regression models. ORs and 95% CIs were estimated separately for heterozygous and homozygous variant Analyses were conducted for each study separately and for all studies combined. All models were adjusted for age to control for a potential residual confounding by imperfect matching. Heterogeneity of effects by study was examined using two different methods. First, we included study site as a fixed effect covariate and evaluated heterogeneity of the association of the rs1271572 SNP with risk by study, using a Wald test of the genotype-study interaction term. Second, we included study site as a random effect using SAS GLIMMIX procedure. No heterogeneity was observed in any of the models, and the results were the same. We also conducted the analysis excluding data from the Hawaii study which initially nominated the SNP for further validation. The association of the rs1271572 with ovarian carcinoma risk by histologic type  was studied using polytomous logistic regression; the estimated ORs among histological types were compared using the Wald test. Heterogeneity of the association of the rs1271572 genotype with risk by age, gravidity, parity, menopausal status, and use of contraceptive and menopausal hormones was evaluated using the Wald test comparing group-specific parameters for the rs1271572 genotype in the logistic regression models. All p-values were based on two-tailed tests. We evaluated statistical significance at the 5% level.Table S1ESR2 rs1271572 genotype and minor allele frequencies (MAF) among non-Hispanic white women by study.(DOC)Click here for additional data file.Table S2ESR2 rs1271572 genotype associations with ovarian cancer risk by study.(DOC)Click here for additional data file.Table S3ESR2 rs1271572 genotype associations with ovarian cancer risk by study stratified by age (≤50 versus >50 years).(DOC)Click here for additional data file.Table S4ESR2 rs1271572 genotype with ovarian carcinoma risk by histological type.Association of the (DOC)Click here for additional data file.Table S5Case ascertainment and selection of controls.(DOC)Click here for additional data file.


IL-4) gene (−1098G and 590T) are associated with BD in the Turkish population. This study was conducted in Turkish patients with BD to determine the frequency of the IL-4 gene 70 bp variable number of tandem repeats (VNTR) variant, and its association with clinical findings.Behçet’s disease (BD) is a systemic vasculitis characterized by inflammatory lesions of the urogenital mucosa, eyes, skin, central nervous system, and joints. Vein thrombosis constitutes the most frequent vascular manifestation of the disease, and may cause such ocular vascular thrombotic events as central retinal vein and central retinal artery thrombosis. Thrombosis is a serious problem, and often leads to irreversible vision loss. Previous studies have shown that genetic factors predispose individuals to BD. Several cytokine genes might play crucial roles in host susceptibility to BD and to thrombophilia. Various polymorphic regions of the interleukin-4  was used in the study. Genomic DNA was isolated and genotyped using PCR assay for the IL-4 genotype distribution  and allele frequencies . When we examined IL-4 genotype frequencies according to the clinical characteristics, we observed a statistically significant association between the P2P2 genotype and deep venous thrombosis (p=0.01). Deep venous thrombosis was also associated with ocular involvement in our study group (p=0.014).There was statistical significance between the groups regarding IL-4 gene 70 bp VNTR polymorphism is associated with susceptibility to development of BD. Deep venous thrombosis is also associated with ocular involvement in BD. The IL-4 gene could be a genetic biomarker in Behçet’s disease in a Turkish study population.Our findings suggest that the  Behçet’s disease (BD) is a chronic multisystem inflammatory disorder characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The common manifestations are recurrent oral and genital ulcers and ocular involvement. Venous or arterial thromboses occur in 7% to 38% of patients . Venous 2, 0.5 U Taq polymerase, 10 mM KCl buffer . Amplification was carried out using primers F5’ AGG CTG AAA GGG GGA AAG C-3’, R5’-CTG TTC ACC TCA ACT GCT CC-3’, with initial denaturation at 95 ºC for 5 min, 30 cycles of denaturation at 94 ºC for 30 s, annealing at 58 ºC for 45 s, extension at 72 ºC for 1 min, and final extension at 72 ºC for 10 min. P1P1 genotype was homozygous wild type, P1P2 genotype heterozygous mutant, P2P2 genotype homozygous mutation type, wild type allele was P1 and mutant type allele was P2, respectively. The PCR products were visualized on three percent agarose gel stained with ethidium bromide. PCR product was of 183 bp for P1 allele and 253 bp for P2 allele. In order to validate the accuracy and reproducibility of this method, each PCR reaction included negative and positive controls. The second PCR was performed to confirm samples whose results were not clear. Also, to confirm the accuracy of the genotyping, repeated analysis was performed on randomly selected samples. No discrepancies were found.The present study included 238 patients with BD and 250 controls, recruited from the Gazi Osmanpaşa University Department of Physical Medicine and Rehabilitation . The ethics committee of Gazi Osmanpaşa University Medical Faculty approved informed consent in accordance with the study protocol. Patients with BD fulfilled the International Criteria of Behçet’s Disease for classification . All pat2 analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A p value smaller than 0.05 (two-tailed) was statistically significant.Analysis of the data was performed using SPSS 15.0  and the OpenEpi Info software package program . Continu2 allele was a 2.3-fold risk factor for BD . When we examined the IL-4 genotype frequencies according to the clinical characteristics, we found a statistically significant association between the P2P2 genotype and deep venous thrombosis according to the genotype frequencies  level was associated with the polymorphism of EPCR gene 6936A/G. The plasma sEPCR level in patients with deep venous thrombosis was higher than that in healthy control subjects [IL-2 , IL-4 , IL-10 , IL-12 (−1188), interferon-γ (5644), transforming growth factor (TGF)-β , and IL-4RA (+1902) polymorphisms, and reported a significantly increased frequency of IL-2 (−330) GG genotype (p<0.001), IL-4 (−33) CC genotype (p<0.001), and TGF-β (codon 10) CC genotype (p=0.004). A significant decrease in the frequency of the IL-4 (−33) TC genotype (p<0.001) was reported in the patient group compared with healthy controls. The genotype CC of TGF-β at codon 10 was also significantly overrepresented in the patient group (p=0.004) [NEMO mutation is a cause of familial occurrence of Behcet’s disease in female patients [protein Z gene and venous thrombosis and other clinical manifestations in Italian patients with BD. However, no associations were found [They also reported that the s for BD . Kurata nd - A26 . Akman end - A26 . Kim et subjects . Shahramp=0.004) . Recent rferon-γ 44, transre found . Increasre found . In addire found .1 allele of the IL-4 gene 70 bp VNTR polymorphism may constitute a risk for developing BD. Several studies have demonstrated that different genes mutations might play an important role in the etiology of BD. Due to limited research on the IL-4 gene in BD, the present study makes an important contribution to the literature. Our study demonstrates that polymorphisms in the IL-4 gene seem to be involved in the susceptibility to BD. Further work is required to confirm these findings in different study groups.In conclusion, our results suggest that possession of the P


Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated to alter the risk of prostate cancer, but the results are controversial.Two investigators independently searched the Medline, and Cochrane Library up to June 7, 2011. Summary odds ratios (OR) and 95% confidence interval (CI) for Ser326Cys polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 10.0.A total of 8 independent studies, including 2584 cases and 3234 controls, were identified. Our analysis suggested that Ser326Cys was not associated with prostate cancer risk in overall population. In the subgroup analysis, we detected the significant association between Ser326Cys polymorphism and decreased prostate risk in mixed population under additive model , recessive model , and Cys allele versus Ser allele . Subanalysis on Caucasian subjects demonstrated that Ser326Cys was not associated with prostate cancer risk.This meta-analysis showed the evidence that hOGG1 Ser326Cys polymorphism was associated with a decreased risk of prostate cancer development in mixed populations. Prostate cancer (PCa) is one of the most common malignant diseases among men. The mechanism of its carcinogenesis, like other cancers, still remains unclear. Multiple environmental and lifestyle factors may increase the risk of PCa, including tobacco use, and a diet poor in fresh fruits and vegetables. However, not all of those who have been exposed to the risk factors will develop PCa, suggesting the inter-individual differences in susceptibility. DNA repair pathways play a critical role in maintaining the genomic integrity in general and specialized functions of cells as well as in the prevention of carcinogenesis, and therefore variations in these genes may lead to higher susceptibility to PCa.8-Oxodeoxyguanosine, the most abundant lesion generated by oxidative stress from the environment and normal cellular metabolism, is highly mutagenic resulting in GC to TA transversion ,2. hOGG1In the past years, the hOGG1 Ser326Cys polymorphism has attracted widespread attention. hOGG1 is abundantly expressed in prostate tissue, the functional consequences of the hOGG1 Ser326Cys polymorphism are strongly debated . One stuTo date, no meta-analysis has been conducted to investigate the association of Ser326Cys polymorphism of hOGG1 gene and PCa. Hence, a meta-analysis based on a total of 8 independent studies was performed, which may provide the evidence for association of hOGG1 Ser326Cys polymorphism with PCa susceptibility.We searched the articles using the terms "hOGG1" or "OGG1", "polymorphism" or "variation", "prostate" and "cancer" in Medline and Cochrane Library, and all eligible studies were detected before June 7, 2011. We evaluated all associated publications to retrieve the most eligible literatures. Their reference lists were hand-searched to find other relevant publications. Of the studies with overlapping data published by the same investigators, only the most recent or complete study was included in this meta-analysis.The following inclusion criteria were used to select literatures for the meta-analysis: (1) Only the case-control studies were considered; (2) The paper should clearly describe PCa diagnoses and the sources of cases and controls; (3) The authors must offer the size of the sample, OR and their 95% CI or the information that can help infer the results in the papers. The exclusion criteria were: (1) none-case-control studies; (2) control population including malignant tumor patients; and (3) duplicated publications.Two investigators reviewed and extracted information from all eligible publications independently, according to the inclusion and exclusion criteria listed above. An agreement was reached by discussion between the two reviewers whenever there was a conflict. The following items were collected from each study: first author's surname, year of publication, statistical data, ethnicity, total number of cases and controls as well as numbers of cases and controls with Ser/Ser, Ser/Cys, and Cys/Cys genotypes, respectively. Different descents were categorized as Caucasian, Asian, African and Mixed, which included more than one ethnic descent.The effect measure of choice was OR with its corresponding 95% CI. The significance of the summary OR was determined with a Z-test and P < 0.05 was considered as statistically significant. In our study, two models of meta-analysis were applied for dichotomous outcomes: the fixed-effects model and the random-effects model. The fixed-effects model assumes that studies are sampled from populations with the same effect size, making an adjustment to the study weights according to the in-study variance. The random-effects model assumes that studies are taken from populations with varying effect sizes, calculating the study weights both from in-study and between-study variances, considering the extent of variation, or heterogeneity. Heterogeneity assumption was checked by Q-test. P ≥ 0.10 for the Q-test indicated lack of heterogeneity among the studies. Either a random-effects model or fixed-effects model was used to calculate pooled effect estimates in the presence or absence of heterogeneity ,17, respFirstly, we examined Ser326Cys genotypes using additive (Cys/Cys vs Ser/Ser), recessive (Cys/Cys vs Ser/Cys + Ser/Ser) and dominant (Cys/Cys + Ser/Cys vs Ser/Ser) genetic models. Then, the comparison of Cys allele with Ser allele  was examined. An asymmetric plot indicates a possible publication bias. The symmetry of the funnel plot was further evaluated by Egger's linear regression test. The significance of the intercept was determined by the t-test suggested by Egger . All statistical tests were performed with Review Manage, version 5.0 and Stata 10.0 using two-sided P-values.8 publications on hOGG1 Ser326Cys genotypes and PCa were identified through literature search and selection based on the inclusion and exclusion criteria . 8 indepThe meta-analysis for association of Ser326Cys polymorphism with PCa in overall population included 8 independent studies with a total of 2584 cases and 3234 controls. The Q-test of heterogeneity was significant and we conducted analyses using random effect models. There was no statistically significant difference in Pca risk between the patients with Cys/Cys genotype and those with Ser/Ser genotype . Similarly, no significant associations were found in the recessive model comparison  and dominant model comparison . In addition, we did not detect the association between Ser326Cys polymorphism and PCa when examining the contrast of Cys versus Ser . In the stratified analysis by ethnicity, significant between-study heterogeneity was detected in all the comparisons in Caucasians, but not in mixed population. For mixed population, there was significant association between Ser326Cys polymorphism and decreased PCa for additive model comparison  of DNA repair pathways. DNA damage generated by different carcinogenic agents or inflammatory process is repaired mostly by BER. Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA. Deficits in repair capacity may lead to genetic instability and carcinogenesis ,19. So aSince the identification of hOGG1 Ser326Cys polymorphism, a number of studies have investigated the genetic effect of this polymorphism on PCa susceptibility, but the results are inconclusive. As a powerful statistical method, meta-analysis can provide a quantitative approach for pooling the results of different researches on the same topic, and for estimating and explaining their diversity ,21. ThisThe results of several studies have suggested that single nucleotide polymorphisms may determine the differences in the risk of PCa between ethnic groups ,23. EthnIn the present study, statistically significant between-study heterogeneity of genotype effect was detected in all different genetic models when all the eligible studies were pooled into the meta-analysis. After subgroup analyses by ethnicity, significant heterogeneity was only detected in Caucasians. The heterogeneity was effectively removed in mixed subgroup. Significant between-study heterogeneity was detected in overall and Caucasian population and we conducted analyses using random effect models. Then we got a wider confidence interval and a larger P-value which may be distorting the meta-analysis. The data showed that no obvious publication bias existed in our meta-analysis.Some limitations of this meta-analysis should be acknowledged. First, controls were not uniformly defined, so selection bias may occur and they may not be representative of the general population. Second, the number of cases and controls in the included studies was relatively low. Third, our result was based on unadjusted estimates, while a more precise analysis should be conducted adjusted by other factors like smoking, drinking status and environmental factors. Fourth, in the subgroup analyses by ethnicity, relatively limited study number and incomplete information for mixed ethnicities made it impossible to perform ethnic subgroup analysis of Africans and Asians. Thus, additional studies are warranted to evaluate the effect of this functional polymorphism on PCa risk in different ethnicities, especially in Africans and Asians. In addition, our analysis did not consider the possibility of gene-gene or SNP-SNP interactions or the possibility of linkage disequilibrium between polymorphisms. Therefore, larger and well-designed studies are needed to further evaluate the association between hOGG1 polymorphism and PCa risk.Our meta-analysis evaluated the association between Ser326Cys polymorphism and PCa risk and revealed that hOGG1 polymorphism Ser326Cys was associated with a statistically significant decrease in PCa risk in mixed population. Due to limitations showed above in this analysis, it is critical that larger and well-designed multicenter studies are needed to confirm our results.hOGG1: human 8-oxoguanine glycosylase 1; PCa: prostate cancer; BER: base excision repair; OR: odds ratio; CI: confidence interval; vs: versus; R: random effect model; F: fixed effect model.The authors declare that they have no competing interests.ZH carried out the publication search, participated in data analysis and drafted the manuscript. XY carried out publication search, and revised the manuscript. ZZ participated in the publication search and helped to draft the manuscript. LL participated performed the statistical analysis. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/11/391/prepub