Variants in endothelial nitric oxide synthase (eNOS) gene in idiopathic infertile Brazilian men

Purpose

In recent years, considerable concern has been expressed about the deleterious effects of reactive oxygen species (ROS) on sperm function, because ROS at high levels is potentially detrimental to sperm function and quality. Nitric oxide (NO) is a powerful anti-oxidant present in seminal plasma. The aim of the study was to analyze the distribution of the of endothelial nitric oxide synthase (eNOS) gene (T-786C, G894T, e 4a/b) polymorphisms in idiopathic infertile Brazilian men and evaluate the possible role of these polymorphisms in sperm count.

Methods

A case–control study was performed comprising 208 infertile men [n = 74 with non-obstructive azoospermia and n = 134 with severe oligozoospermia] and 201 fertile men as controls. Genotyping of eNOS polymorphisms was performed by real time (T-786C and G894T) and conventional PCR (4a/b). The results were analyzed statistically and a p-value < 0.05 was considered significant.

Results

According to the sperm count, relatively similar eNOS polymorphism genotypes and allele frequencies were found among the groups. Combined genotypes of the eNOS polymorphisms did not identify a haplotype associated with idiopathic infertility, even when the patients were separated in non-obstructive azoospermia or severe oligozoospermia.

Conclusion

In conclusion, the findings demonstrate that, in Brazilian population studied, genetic variations, T-786C, G894T, and e 4a/b, of the eNOS gene are not associated with male infertility.     

Endothelial Nitric Oxide Synthase (eNOS) gene polymorphisms in spontaneously aborted embryos

Endothelium-derived nitric oxide (NO) is synthesized from L-arginine by endothelial nitric oxide synthase (eNOS) encoded by the eNOS gene on chromosome 7. The effects of the eNOS polymorphisms with the risk of spontaneous pregnancy losses are conflicting. In this study, we investigated the association of the eNOS genotypes with spontaneously aborted embryos in Koreans. Case-control studies were performed to evaluate the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and spontaneously aborted embryos. Ninety-nine spontaneously aborted fetuses at <20 weeks of gestational age and 103 child controls and 282 adult controls. Genotype frequency of three eNOS gene polymorphisms, ?786T>C, VNTR in intron 4 (4a4b), and 894G>T in spontaneously aborted embryos was surveyed. The frequencies of ?786TC and CC genotypes in aborted embryos were significantly higher than in both child and adult controls. The frequencies of 4a4a homozygote of VNTR polymorphism in intron 4 and TT homozygote of 894G>T polymorphisms were also higher in aborted embryos than in adult controls. Haploptype analysis suggested that ?786T>C polymorphism was a possible risk factor for spontaneously aborted embryos. eNOS gene polymorphisms, ?786T>C, VNTR in intron 4 (4a4b), and 894G>T, are associated with the risk of spontaneously aborted fetuses.     

The polymorphism for endothelial nitric oxide synthase gene,the level of nitric oxide and the risk for pre-eclampsia: A meta-analysis

Endothelial NO, which is synthesized by endothelial nitric oxide synthase (eNOS), has been reported to be related with the occurrence of pre-eclampsia (PE). However, the polymorphisms of eNOS (− 786 T > C, 4b/a and G894T), the level of nitric oxide and the risk of PE remain unclear. Thus we performed this meta-analysis to determine the associations between them in order to predict the risk for PE and interference with PE development in the early period of antenatal care. All studies investigating the associations between PE risk and polymorphisms of eNOS, or PE risk and serum concentration of NO were reviewed. Finally, 29 studies were included, involving 11 for − 786 T > C, 11for 4b/a, and 22 for G894T polymorphisms and PE risk. In the overall analysis, − 786 T > C polymorphism was found to be related with increased PE risk in the dominant model (OR = 1.17, 95% CI = 1.02-1.35). a allele for 4b/a suffers the high risk of PE (OR = 1.46, 95% CI = 1.01–2.10). In the subgroup analysis, significantly increased risk was detected among Europeans for − 786 T > C polymorphism (OR = 1.40, 95%CI = 1.14–1.73).However, no significant association was detected for G894T polymorphism in the overall and subgroup analysis. The comprehensive evaluation of 9 available studies indicated that serum NO level was significantly decreased in case group (SMD = − 0.96 umol/mL, 95%CI = − 1.80, − 0.12 umol/mL).Hence, we concluded that eNOS gene − 786 T > C and 4b/a except for G894T polymorphisms were contributed significantly to PE risk, especially for Europeans, and a low NO concentration in serum increased the risk for PE.     

Promoter polymorphisms of pri-miR-34b/c are associated with hepatocellular carcinoma

Background

Numerous studies have focused on the association between miR-34 family members, which are direct p53 targets, and carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). This study aimed to assess whether polymorphisms in the single-nucleotide polymorphism miR-34b/c T>C (rs4938723) and TP53 Arg72Pro (rs1042522) increase the risk of HCC and influence outcome in patients with HCC.

Patients and methods

We enrolled 157 HCC patients and 201 cancer-free control subjects from the Korean population. MicroRNA polymorphisms were genotyped using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method.

Results

We found that the miR-34b/c TC + CC frequency was significantly higher in HCC patients than in controls (adjusted odds ratio [AOR]: 1.580; 95% confidence interval [CI]: 1.029–2.426). The miR-34b/c CC-TP53 Arg/Arg combination significantly increased the risk of HCC (AOR: 13.644; 95% CI: 1.451–128.301). The SNPs miR-34b/c T>C and TP53 Arg72Pro(G>C) had no influence on survival of HCC patients.

Conclusions

Our findings suggest that loss of the T allele in miR-34b/c T>C, and the miR-34b/c CC-TP53 Arg/Arg combination increases the risk of HCC in the Korean population.     

Polymorphisms of folate metabolism-related genes and survival of patients with colorectal cancer in the Korean population

Background

5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival.

Patients and methods

We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C > T and 1298A > C, and RFC1 − 43T > C, 80G > A, and 696C > T. Using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS).

Results

The combined TS 1494 0bp6bp + 6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 − 43CC and 80AA genotypes were associated with favorable OS.

Conclusions

Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings.     

Association between the − 786T>C 1polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease: A systematic review and meta-analysis

Background

A variety of studies have evaluated the association between the − 786T>C polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease (CAD). However, the results remain conflicting. To better understand the role of eNOS − 786T>C polymorphism in CAD risk, we conducted a comprehensive systematic review and meta-analysis.

Methods

Case–control, cohort or cross-sectional studies evaluating the association between eNOS − 786T>C polymorphism and CAD risk were searched in electronic databases of PubMed, ISI Web of Knowledge, Medline, Embase and Google Scholar Search (up to January 2013). Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between eNOS − 786T>C polymorphism and CAD risk. Statistical analysis was performed with Review Manager 5.0 and STATA12.0.

Results

Twenty-four studies were analyzed between 6192 CAD cases and 9281 healthy controls. The combined results of overall analysis showed significant positive associations between CAD risk and eNOS − 786T>C polymorphism in dominant model (OR = 1.45, 95% CI = 1.27–1.65), recessive model (OR = 1.37, 95% CI = 1.20–1.56), homozygote comparison (OR = 1.64, 95% CI = 1.31–2.04), heterozygote comparison (TC vs. TT, OR = 1.39, 95% CI = 1.23–1.57; CC vs. TC, OR = 1.20, 95% CI = 1.04–1.37) and allele comparison (OR = 1.35, 95% CI = 1.21–1.50). On subgroup analysis based on the ethnicity of population (Caucasians, Asians and others), significant differences were found in all genetic models for Caucasians, similar associations existed in Asians except heterozygote comparison (CC vs. TC). However, the associations were only found in dominant model, heterozygote comparison (TC vs. TT) and allele comparison for the populations named others.

Conclusions

Our investigations demonstrate the significant associations between eNOS − 786C>T polymorphism and CAD risk, and this polymorphism might become an early marker for the risk evaluation of CAD.     

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the −786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects.A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and −786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR.There was significant linkage disequilibrium between the three NOS3 polymorphisms (p < 0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not −786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24–15.41; p = 0.021, dominant model OR: 1.66, 95%CI: 1.14–2.42); p = 0.007, and recessive model OR: 3.85, 95%CI: 1.10–13.47; p = 0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR = 12.05, p = 0.010) was a risk factor of MI after controlling for classical risk factors.These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.     

Association of functional FEN1 genetic variants and haplotypes and breast cancer risk

Aim

As a tumor suppressor, FEN1 plays an essential role in preventing tumorigenesis. Two functional germline variants (-69G > A and 4150G > T) in the FEN1 gene have been associated with DNA damage levels in coke-oven workers and multiple cancer risk in general populations. However, it is still unknown how these genetic variants are involved in breast cancer susceptibility.

Methods

We investigated the association between these polymorphisms and breast cancer risk in two independent case–control sets consisted of a total of 1100 breast cancer cases and 1400 controls. The influence of these variations on FEN1 expression was also examined using breast normal tissues.

Results

It was found that the FEN1-69GG genotypes were significantly correlated to increased risk for developing breast cancer compared with the -69AA genotype in both sets [Jinan set: odds ratios (OR) = 1.41, 95% confidence interval (CI) = 1.20–1.65, P = 1.9×10^− 5; Huaian set: OR = 1.51, 95% CI = 1.22–1.86, P = 1.7×10^− 4]. Similar results were observed for 4150G > T polymorphism. The genotype–phenotype correlation analyses demonstrated that the -69G or 4150G allele carriers had more than 2-fold decreased FEN1 expression in breast tissues compared with -69A or 4150T carriers, suggesting that lower FEN1 expression may lead to higher risk for malignant transformation of breast cells.

Conclusion

Our findings highlight FEN1 as an important gene in human breast carcinogenesis and genetic variants in FEN1 confer susceptibility to breast cancer.     

The role of endothelial nitric oxide synthase (eNOS) T‐786C,G894T,and 4a/b gene polymorphisms in the risk of idiopathic male infertility

A considerable number of infertile men have no known mechanism for their infertility. This study aims to examine if there is an association between endothelial nitric oxide synthase (eNOS) T‐786C, G894T, and 4a/b gene polymorphisms and idiopathic male infertility. Three hundred fifty‐two men with idiopathic infertility (mean age 32.4 ± 11.4 years) and 356 healthy controls (mean age 33.2 ± 11.6 years) with documented fertility were recruited in this study. Genotypes for T‐786C, G894T, and 4a/b gene polymorphisms were identified by the polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) analysis. The eNOS ?786CC genotype (0.310 vs. 0.081; odds ratio (OR), 3.64; 95% confidence interval (CI), 2.28–4.46; P = 0.001), 894TT genotype (0.131 vs. 0.006; OR, 3.62; 95% CI, 2.68–4.87; P = 0.001) and 4aa genotype (0.128 vs. 0.009; OR, 2.82; 95% CI, 1.88–3.89; P = 0.004) were significantly more frequent in infertile subjects. Furthermore, there was a significant difference between the group of infertile patients with azoospermia and oligoasthenoteratozoospermia (OAT) when compared by genotype distribution (?786CC vs. 786TT, 894TT vs. 894GG, and 4aa vs. 4bb) (all P < 0.01). We also found an association between the eNOS “?786C,” “894T,” and “a” alleles and an increased risk of poor semen parameters. Our data revealed a significant relationship between eNOS genotypes and the phenotype of infertility. Mol. Reprod. Dev. 77: 720–727, 2010. © 2010 Wiley‐Liss, Inc.     

A genetic variant in the promoter of APE1 gene (− 656 T > G) is associated with breast cancer risk and progression in a Chinese population

Background/aims

APE1 is an important DNA repair protein in the base excision repair pathway. Genetic variations in APE1 have been suggested to influence individuals' susceptibility to human malignancies. The present study was aimed to investigate the associations between two functional polymorphisms in APE1 (− 656 T > G and 1349 T>G) and breast cancer risk.

Methods

We genotyped the two polymorphisms in a case-control study of 500 breast cancer patients and 799 age-matched cancer-free controls using the TaqMan method. Unconditional logistic regression adjusted for potential confounding factors was used to assess the associations.

Results

We found that the variant genotypes of the − 656 T>G were significantly associated with decreased breast cancer risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.56–0.91], and the protective effect of this polymorphism was more predominant among the subgroups of younger subjects (< 52 years) (OR = 0.65, 95% CI = 0.46–0.92). Besides, we found that the variant genotypes were associated with less frequent lymph node metastasis (P = 0.020, OR = 0.64, 95% CI = 0.44–0.94). We did not observe any significant association between the 1349 T>G polymorphism and breast cancer risk.

Conclusion

Our results suggest that the APE1 − 656 T>G but not the 1349 T>G polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population. Large population-based prospective studies are required to validate these findings.     

Association study of polymorphisms in the receptor for advanced glycation end-products (RAGE) gene with susceptibility and prognosis of heart failure

Background

Functional polymorphisms in the receptor for advanced glycation end-products (RAGE) gene have been implicated in several vascular diseases. However, to date, no study investigated the association of RAGE polymorphisms with heart failure (HF).

Objective

In this study we tested the hypothesis that the 63-bp insertion/deletion, the − 374T > A (rs1800624) and the − 429T > C (rs1800625) polymorphisms in the RAGE gene might be associated with susceptibility to HF and could predict all-cause mortality in Brazilian outpatients with left ventricular systolic dysfunction.

Methods

A total of 273 consecutive HF patients (196 Caucasian- and 77 African-Brazilians) and 334 healthy blood donors (260 Caucasian- and 74 African-Brazilians) were enrolled in a tertiary care university hospital. Genotyping of RAGE polymorphisms was done by polymerase chain reaction (PCR) or PCR followed by enzyme restriction analysis.

Results

The allele, genotype and haplotype frequencies of − 374T > A and − 429T > C polymorphisms were not significantly different between HF patients and healthy blood donors in both ethnic groups. However, among African-Brazilians, the frequency of carriership of the del allele was lower in HF patients than in blood donors (2.6% vs 12.2%, respectively, p = 0.008). Patients were followed-up for a median of 38 months and the survival analysis did not reveal a consistent association between RAGE polymorphisms and all-cause death in both ethnic groups.

Conclusion

The − 374T > A and − 429T > C polymorphisms in the RAGE gene were not associated with the susceptibility and prognosis of HF. Notwithstanding, the 63-bp ins/del polymorphism might be involved in the susceptibility to HF in African-Brazilians.     

An updated meta-analysis of endothelial nitric oxide synthase gene: three well-characterized polymorphisms with hypertension

Background

Numerous individually underpowered association studies have been conducted on endothelial nitric oxide synthase (eNOS) genetic variants across different ethnic populations, however, the results are often irreproducible. We therefore aimed to meta-analyze three eNOS widely-evaluated polymorphisms, G894T (rs1799983) in exon 7, 4b/a in intron 4, and T−786C (rs2070744) in promoter region, in association with hypertension from both English and Chinese publications, while addressing between-study heterogeneity and publication bias.

Methods

Data were analyzed using Stata software (version 11.0), and random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Publication bias was weighed using the Egger''s test and funnel plot.

Results

There were total 19284/26003 cases/controls for G894T, and 6890/6858 for 4b/a, and 5346/6392 for T−786C polymorphism. Overall comparison of allele 894T with 894G in all study populations yielded a 16% increased risk for hypertension (odds ratio [OR] = 1.16; 95% confidence interval [95% CI]: 1.07–1.27; P = 0.001), and particularly a 32% increased risk (95% CI: 1.16–1.52; P<0.0005) in Asians and a 40% increased risk (95% CI: 1.19–1.65; P<0.0005) in Chinese. Further subgroup analyses suggested that published languages accounted for the heterogeneity for G894T polymorphism. The overall OR of allele 4a versus 4b was 1.29 (95% CI: 1.13–1.46; P<0.0005) in all study populations, and this estimate was potentiated in Asians (OR = 1.42; 95% CI: 1.16–1.72; P<0.0005). For T−786C, ethnicity-stratified analyses suggested a significantly increased risk for −786C allele (OR = 1.25; 95% CI: 1.06–1.47; P = 0.007) and −786CC genotype (OR = 1.69; 95% CI: 1.20–2.38; P = 0.003) in Whites. As an aside, the aforementioned risk estimates reached significance after Bonferroni correction. Finally, meta-regression analysis on other study-level covariates failed to provide any significance for all polymorphisms.

Conclusion

We, via a comprehensive meta-analysis, ascertained the role of eNOS G894T and 4b/a polymorphisms on hypertension in Asians, and T−786C polymorphism in Whites.     

Association between 1603C>T polymorphism of DBH gene and bipolar disorder in a Turkish population

Objectives

Dopamine-β-hydroxylase (DBH) is the enzyme responsible for the conversion of dopamine (DA) to norepinephrine (NE, noradrenaline) which is a key neurotransmitter in the central and peripheral nervous systems. Bipolar disorder is a major psychiatric disorder. The present study was designed to explore the associations of polymorphisms of DBH gene in Turkish patients with bipolar disorder.

Methods

− 1021C>T (rs1611115) polymorphism in promoter region, 444G>A (rs1108580) polymorphism in exon 2 and 1603C>T (rs6271; C535R) polymorphism in exon11 of DBH gene were analyzed in 106 patients with bipolar disorder and 106 healthy subjects by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.

Results

The results showed statistically significant associations for genotypic and allelic distribution between the 1603C>T polymorphism and bipolar disease (p = 0.0012 and p = 0.034, respectively). There was no association observed between the genotype and allelic frequencies for − 1021C>T and 444G>A polymorphisms and bipolar disorder.

Conclusions

Our data suggests that the 1603C>T polymorphism of the DBH gene is associated with susceptibility to bipolar disorder in a Turkish population.     

Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: A meta-analysis

Objective

The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection.

Methods

A literature search on articles published before December 1st, 2012 was conducted in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software.

Results

Eight studies were eligible for inclusion in this meta-analysis, including five cross-sectional studies on individual's response to hepatitis B vaccine and three case–control studies on HBV infection risk. The meta-analysis results showed that the T allele of rs2243250, the T allele of rs2070874, and the C allele of rs2227284 in IL4 gene were associated with high responses to hepatitis B vaccine. Further subgroup analysis by ethnicity showed that there was a significant association between IL4 genetic polymorphisms and an individual's responses to hepatitis B vaccine among Asian populations, but similar association was not found among Caucasian populations. However, there was no evidence indicating a correlation between IL4 genetic polymorphism and susceptibility to HBV infection.

Conclusion

Our current meta-analysis suggests that rs2243250, rs2070874 and rs2227284 polymorphisms in IL4 gene may play an important role in determining the response to hepatitis B vaccine, especially among Asian populations. However, further studies are still needed to evaluate the associations between IL4 genetic polymorphisms and HBV infection risk.     

An updated meta-analysis of endothelial nitric oxide synthase gene: Three well-characterized polymorphisms with ischemic stroke

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of ischemic stroke (IS), but the results are still debatable. A meta-analysis was performed to investigate the association between the eNOS gene polymorphisms in IS risk. Case–control studies on the association between the G894T, T-786C, and 4b/a polymorphisms and IS were searched up to July 2012, and the genotype frequencies in the control group were found to be consistent with the Hardy–Weinberg equilibrium (HWE). The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Meta-regression was used to explore the potential sources of heterogeneity. Funnel plots and Egger's test was used to estimate small study biases, and heterogeneity was assessed by chi-square-based Q-test and I² test. There were total 6537/6475 cases/controls for G894T, 3459/3951 cases/controls for 4b/a, and 2125/2673 cases/controls for T-786C polymorphism. For G894T and 4b/a, a significant association of 894 T allele and 4a allele with increased risk of IS was found in Asians (TT + GT vs. GG: p < 0.00001, OR = 1.60, 95% CI = 1.38–1.79, P_{heterogeneity} = 0.11; aa + ba vs. bb: P < 0.00001, OR = 1.60, 95% CI = 1.30–1.97, P_{heterogeneity} = 0.02), but not in Caucasians (TT + GT vs. GG: P = 0.60, OR = 0.94, 95% CI = 0.75–1.19, P_{heterogeneity} = 0.002; aa + ba vs. bb: P = 0.13, OR = 0.81, 95% CI = 0.62–1.06, P_{heterogeneity} = 0.63). For T-786C polymorphism, there were no significant differences in genotype distribution between IS and control in Asians (CC + TC vs. TT: P = 0.15, OR = 1.14, 95% CI = 0.95–1.37, P_{heterogeneity} = 0.94) and in Caucasians (CC + TC vs. TT: P = 0.72, OR = 0.96, 95% CI = 0.75–1.22, P_{heterogeneity} = 0.53). This analysis provides strong evidence that the eNOS T-786C gene polymorphism is not associated with IS, the G894T and 4b/a polymorphisms might be associated with IS, at least in Asians.     

Association of IL-6 − 174G > C and − 572C > G polymorphisms with risk of young ischemic stroke patients

Aim

To investigate the association between interleukin-6 (IL-6) − 174G > C and − 572C > G polymorphisms and risk for ischemic stroke (IS) in young patients.

Methods

We genotyped IL-6  − 174G > C and − 572C > G in a case–control study of 430 young IS patients and 461 control subjects. An unconditional multiple logistical regression model was used to calculate the effects of IL-6 − 174G > C and − 572C > G polymorphisms on IS risk.

Results

Higher body mass index, diabetes, hypertension, obesity, and smoking were associated with risk of ischemic stroke. Multivariate regression analyses showed that subjects carrying the − 174CC genotype (OR = 1.69, 95% CI = 1.16–2.57) and C allele (OR = 1.37, 95% CI = 1.09–1.67) had a small but significant increased risk of IS. Similarly, those carrying the − 572GG genotype (OR = 2.12, 95% CI = 1.18–3.82) and G allele (OR = 1.43, 95% CI = 1.14–1.83) had a moderate increased risk of IS. We found the − 174G > C and − 572C > G polymorphisms interact with hypertension and obesity.

Conclusion

Our results suggest that polymorphisms in IL-6 − 174G > C and − 572C > G are associated with IS risk in young patients, and that these polymorphisms interact with hypertension, obesity and etiologic subtypes. These findings could be helpful in identifying individuals at increased risk for developing IS.     

Tumor necrosis factor alpha − 308G>A, − 863C>A, − 857C>T gene polymorphisms and tuberculosis susceptibility: A meta-analysis

Background/aims

A large number of studies have shown that polymorphisms in the tumor necrosis factor-α (TNF-α, TNFA) gene are implicated in susceptibility to tuberculosis (TB). However, the results are inconsistent. We performed this meta-analysis to estimate the association between polymorphisms in the TNFA gene and TB susceptibility.

Methods

Relevant studies published before March 2012 were identified by searching PubMed, ISI web of knowledge, EBSCO and CNKI. The strength of relationship between the TNFA gene and TB susceptibility was assessed using odds ratios (ORs).

Results

A total number of twenty-three case–control studies including 3630 cases and 4055 controls were identified referring to three previously chosen single-nucleotide polymorphisms (SNPs): − 308G>A, − 863C>A and − 857C>T. No association was found between − 308G>A, − 863C>A and TB susceptibility: − 308G>A (GG + GA vs. AA): OR 0.85, 95%CI: 0.55–1.30, P = 0.44; − 863C>A (CC + CA vs. AA): OR 0.93, 95%CI: 0.84–1.81, P = 0.83. Increased risk of TB was associated with − 857C>T in the dominant genetic model (CC + CT vs. TT: OR 2.13, 95%CI: 1.25–3.63, P = 0.01), the heterozygote comparison (CT vs. TT: OR 2.69, 95%CI: 1.44–5.02, P = 0.00) and the homozygote comparison (CC vs. TT: OR 2.08, 95%CI: 1.22–3.53, P = 0.01) in Asian subjects.

Conclusion

There is an increased association between TNFA − 857C>T polymorphism and TB risk among Asian subjects. No association was found between − 308G>A and − 863C>A with TB risk. Due to several limitations in the present study, well-designed epidemiological studies with large sample size among different ethnicities should be performed in the future.     

SCN1A rs3812718 polymorphism and susceptibility to epilepsy with febrile seizures: A meta-analysis

Background

Evidence showed that the SCN1A IVS5N+5G>A polymorphism might be associated with susceptibility to epilepsy with febrile seizures (EFS), however, the published data were inconclusive. Therefore, a meta-analysis was performed to estimate the overall EFS risk with the polymorphism.

Methods

The PubMed and Medline were searched up to March, 2013 for studies on the association between SCN1A IVS5N+5G>A polymorphism and EFS risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by means of a genetic model free approach. The heterogeneity and sensitivity of each report and the publication bias were also performed. All the statistical analyses were done using the STATA 11.0 software.

Result

A total of 6 studies with 2719 cases and 2317 controls met the selection criteria. We found significant association between SCN1A polymorphism and EFS (A vs. G: OR = 1.498, 95%CI = 1.138–1.972; AA vs. GG: OR = 2.292, 95%CI = 1.620–3.243; AG vs. GG: OR = 1.414, 95%CI = 1.010–1.978; recessive model: OR = 1.747, 95%CI = 1.119–2.728 and dominant model: OR = 1.730, 95%CI = 1.259–2.376). When compared with the epilepsy without febrile seizure (EWFS), the subgroup analysis stratified by ethnicity showed that the SNP was significantly associated with EFS in Caucasian (A vs. G: OR = 1.505, 95%CI = 1.218–1.861; AA vs. GG: OR = 2.081, 95%CI = 1.358–3.189; recessive model: OR = 1.715, 95%CI = 1.273–2.310 and dominant model: OR = 1.625, 95%CI = 1.096–2.410), but not in Indian and Chinese. When applying Bonferroni correction (significance was set at 0.05/20), the Caucasian still has robust association with EFS and epilepsy.

Conclusion

The present meta-analysis suggests that SCN1A IVS5N+5G>A polymorphism is a risk factor of EFS and epilepsy, especially in Caucasian.     

The T-786C,G894T,and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in prostate cancer cases

In previously conducted some studies it has been revealed that nitric oxide (NO) and nitric oxide synthase (NOS) system play a significant role in carcinogenesis. Nitric oxide (NO) is regulated by endothelial nitric oxide synthase (eNOS) enzyme which is one of the isoenzymes of NO synthase (NOS). In this study we have tried to come to a conclusion about whether eNOS gene T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms might be considered as a risk factor causing prostate cancer (PCa) or not. A total of 200 subjects were included in this research. 84 patients with PCa (mean age 70.0 ± 6.4) and 116 healthy controls (mean age 69.9 ± 7.5) were recruited in this case-control study. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (QIAGEN GmbH, Maryland, USA), according to the manufacturer’s guidelines. The T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms were amplified using polymerase chain reation (PCR), detected by restriction fragment length polymorphism (RFLP). For T-786C polymorphism CC genotype [odds ratio (OR): 0.34, 95% confidence interval (CI): 0.15–0.78, P = 0.009)] and allele frequency (OR: 0.631, CI: 0.421–0.946, P = 0.026) is significant for control. In patients with PCa eNOS G894T polymorphism, both GT (OR: 0.069, CI: 0.027–0.174; P = 0.0001) and TT (OR: 0.040, CI: 0.013–0.123; P = 0.0001) genotype distribution, and also T allele frequency (OR: 0.237, CI: 0.155–0.362, P = 0.0001) were considered significant statistically. While genotype distribution for the other polymorphism eNOS, intron 4 VNTR (4a/b), is insignificant statistically, “a” allele frequency was found out to be significant (OR: 2.223, CI: 1.311–3.769, P = 0.003). In this study we indicated that genotype and allele frequencies of eNOS T-786C and G894T polymorphisms are statistically significant in patients with PCa. eNOS T-786C and G894T polymorphisms may be associated with PCa susceptibility in the Turkish population. In contrast, intron 4 VNTR (4a/b) polymorphism may not be related to PCa susceptibility in these patients.