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.     

Genetic Association of rs1800780 (A→G) Polymorphism of the eNOS Gene with Susceptibility to Essential Hypertension in a Chinese Han Population

To investigate the association of eNOS gene polymorphism with essential hypertension in the Chinese Han population, we examined polymorphisms of the rs2070744 (T→C), rs1800780 (A→G), and rs3918181 (A→G) loci. The results demonstrated that the genotypic frequency at the rs1800780 (A→G) locus was significantly different between patients with essential hypertension and the control cohorts (P < 0.05); while genotypic frequencies and allelic frequencies at rs2070744 (T→C) and rs3918181 (A→G) loci had no statistical difference between the patient group and controls (P > 0.05). In addition, haplotype analysis found a statistically significant difference for haplotype TGA, with OR (95% CI) of 1.549 (1.116–2.150) (P < 0.05). These findings suggest that polymorphism of rs1800780 (A→G) in the eNOS gene may be one of the most important genetic factors associated with essential hypertension susceptibility, and those who have haplotype TGA may be at risk to develop essential hypertension.     

Endothelial Nitric Oxide Synthase Gene Minisatellite Polymorphism in Populations of the Volga–Ural Region and Analysis of Its Association with Myocardial Infarction and Essential Hypertension

The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene (eNOS) in populations of the Volga–Ural region was studied by means of polymerase chain reaction. In Russians and Tatars, the possible association of this polymorphism with coronary heart disease complicated by either myocardial infarction or by essential hypertension was examined. Russians with essential hypertension associated with hypertrophy of the left ventricle displayed a statistically significant increase of the eNOS4A/Bgenotype and theAallele frequencies along with the decrease of the frequencies of the eNOS4B/Bgenotype and the Ballele. In Tatars survived from myocardial infarction and with the risk of cardiovascular diseases (smoking or burdened heredity), a statistically significant increase of the frequencies of the eNOS4A/Bgenotype and the Aallele was observed. Thus, in Russians the eNOS4A/Bgenotype was associated with the development of essential hypertension, while in Tatars it was associated with the risk of myocardial infarction.     

Association of eNOS polymorphisms (-786T>C, 4a4b, 894G>T) with colorectal cancer susceptibility in the Korean population

Background

Polymorphisms of endothelial nitric oxide synthases (eNOS) have been shown to be associated with cancer susceptibility. However, the results of such studies are conflicting to date. We investigated whether polymorphisms of the eNOS gene correlated with patients with colorectal cancer (CRC), relative to healthy individuals.

Patients and methods

In the present study, we analyzed three polymorphisms of eNOS (-786T>C, 4a4b, and 894G>T) in 509 healthy controls and 528 patients with CRC. The genotyping of eNOS polymorphisms was performed using polymerase chain reaction or polymerase chain reaction–restriction fragment length polymorphism assays.

Results

We found that the TC+CC genotype of the -786T>C polymorphism was significantly associated with an increased risk of CRC compared with the TT genotype. Similarly, the GT+TT genotype of the 894G>T polymorphism was associated with an increased susceptibility to CRC. However, no evidence was found for any association between the 4a4b polymorphism and CRC risk. In addition, the C/4b/G (-786T>C/4a4b/894G>T) haplotype was significantly associated with increased risk of CRC and C/4b/T (-786T>C/4a4b/894G>T) haplotype was only detected in CRC patients.

Conclusions

Our study suggests that the eNOS -786T>C and 894G>T polymorphisms may be associated with the development of CRC in the Korean population.     

Risk conferred by FokI polymorphism of vitamin D receptor (VDR) gene for essential hypertension

BACKGROUND:

The vitamin D receptor (VDR) gene serves as a good candidate gene for susceptibility to several diseases. The gene has a critical role in regulating the renin-angiotensin system (RAS) influencing the regulation of blood pressure. Hence determining the association of VDR polymorphisms with essential hypertension is expected to help in the evaluation of risk for the condition.

AIM:

The aim of this study was to evaluate association between VDRFok I polymorphism and genetic susceptibility to essential hypertension.

MATERIALS AND METHODS:

Two hundred and eighty clinically diagnosed hypertensive patients and 200 normotensive healthy controls were analyzed for Fok I (T/C) [rs2228570] polymorphism by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype distribution and allele frequencies in patients and controls, and odds ratios (ORs) were calculated to predict the risk for developing hypertension by the individuals of different genotypes.

RESULTS:

The genotype distribution and allele frequencies of Fok I (T/C) [rs2228570] VDR polymorphism differed significantly between patients and controls (χ² of 18.0; 2 degrees of freedom; P = 0.000). FF genotype and allele F were at significantly greater risk for developing hypertension and the risk was elevated for both the sexes, cases with positive family history and habit of smoking.

CONCLUSIONS:

Our data suggest that VDR gene Fok I polymorphism is associated with the risk of developing essential hypertension     

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk

BACKGROUND:

Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension.

METHODS:

In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension.

RESULTS:

No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group.

CONCLUSIONS:

We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene–gene–environment interactions may generate more conclusive claims about the molecular genetics of hypertension.     

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.     

Endothelial Nitric Oxide Synthase Gene G894T Polymorphism and Myocardial Infarction: A Meta-Analysis of 34 Studies Involving 21068 Subjects

Background

Researches have revealed that the endothelial nitric oxide synthase (eNOS) gene G894T polymorphism is associated with the risk of Myocardial infarction (MI), but the results remain conflicting.

Objective and Methods

A meta-analysis was conducted to investigate the association between eNOS G894T polymorphism and MI. Published studies from PubMed, Embase, CNKI and CBM databases were retrieved. The pooled odds ratios (ORs) for the association between eNOS G894T polymorphism and MI and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed- effect model.

Results

A total of 34 studies including 8229 cases and 12839 controls were identified for the meta-analysis. The eNOS G894T polymorphism was significantly associated with MI under a homozygous genetic model (OR = 1.41, 95% CI = 1.08–1.84; P = 0.012), a recessive genetic model (OR = 1.35, 95% CI = 1.06–1.70; P = 0.014), a dominant genetic model (OR = 1.18, 95% CI = 1.04–1.34; P = 0.009). In the subgroup analysis by ethnicity (non-Asian and Asian), no significant association was observed between eNOS G894T polymorphism and MI risk among non-Asians (P>0.05), but a positive significant association was found among Asians (P<0.05).

Conclusions

The eNOS G894T polymorphism is associated with increased MI risk in Asians. The results indicate that ethnicity plays important roles in the association between eNOS G894T polymorphism and MI.     

Association of the K173R variant and haplotypes in the aldosterone synthase gene with essential hypertension

Aldosterone synthase plays an important role in determining the levels of aldosterone secretion. Polymorphisms of the aldosterone synthase gene (CYP11B2) are suggested to be associated with essential hypertension. In this study, we examined associations of CYP11B2 polymorphisms [?344T/C, K173R and intron 2 conversion (IC)] with Korean hypertensive patients. Three hundred and forty patients with hypertension and 515 healthy normotensive subjects were studied. CYP11B2 polymorphisms in the subjects were analyzed by polymerase chain reaction–restriction fragment length polymorphism techniques. Of the three polymorphisms studied, we observed a significant difference in the mutant genotype of K173R polymorphism between the hypertensive and normotensive groups (P = 0.03). Several haplotype frequencies composed of three polymorphisms were also associated with hypertension susceptibility. Association between the K173R polymorphism and values of BMI, HDL-cholesterol and WC was found in the hypertensive group. However, no associations of ?344T/C and IC polymorphisms were found with the risk of hypertension and clinical parameters. Based on these results, the K173R variant and haplotypes of the CYP11B2 gene might affect hypertension susceptibility.     

Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibility to knee osteoarthritis

Objective

Interleukin-4 (IL-4) is a strong chondroprotective cytokine and polymorphisms within this gene may be a risk factor for osteoarthritis (OA). We aimed to investigate genotype and allele frequencies of IL-4 gene intron 3 variable number of tandem repeats (VNTR) polymorphism in patients with knee OA in a Turkish population.

Methods

The study included 202 patients with knee OA and 180 healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers followed by restriction fragment length polymorphism (RFLP) analysis.

Results

Our result show that there was statistically significant difference between knee OA patients and control group with respect to IL-4 genotype distribution and allele frequencies (p = 0.000, OR: 0.20, 95% CI: 0.10–0.41, OR: 0.22, 95% CI: 0.12–0.42, respectively).

Conclusions

Our findings suggest that there is an association of IL-4 gene intron 3 VNTR polymorphism with susceptibility of a person for development of knee OA. As a result, IL-4 gene intron 3 VNTR polymorphism could be a genetic marker in OA in a Turkish study population. This is the first association study that evaluates the associations between IL-4 gene VNTR polymorphism and knee OA.     

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.     

The association between Interleukin (IL)-4 gene intron 3 VNTR polymorphism and alopecia areata (AA) in Turkish population

Objective

Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease of hair follicles mediated by T cells. As immunological and genetic factors have been implicated in the pathogenesis of AA, the purpose of the present study was to investigate possible associations between the functional Interleukin (IL)-4 gene intron 3 VNTR polymorphism and AA susceptibility and disease progression in Turkish population.

Methods

The study group consisted of 116 unrelated patients with AA and 125 unrelated healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers.

Results

No association was observed between AA patients and controls according to genotype distribution (p = 0.051). The allele distribution of IL-4 gene intron 3 VNTR polymorphism was statistically different between AA patients and control group (p = 0.026). The frequency of P1 allele in patients was significantly higher than that in the control group. When the P2P2 genotype was compared with P1P2 + P1P1 genotypes, a statistically significant difference was observed between patients and controls (p = 0.036). Intron 3 VNTR polymorphism in the IL-4 gene was found to be associated with AA susceptibility in Turkish population.

Conclusion

The results suggest that IL-4 VNTR polymorphism in the intron 3 region may be a risk factor for the development of AA among Turkish population. This is the first to report that intron 3 VNTR polymorphism in the IL-4 gene is associated with AA susceptibility.     

Correlation and Identification of Variable number of Tandem repeats of eNOS Gene in Coronary artery disease (CAD)

Endothelium-derived nitric oxide (NO) is synthesized from l-arginine by endothelial nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in South Indian patients. We investigated the polymorphisms in the 27 base-pair tandem repeats in intron4 of the eNOS gene in 100 unrelated CAD patients with positive coronary angiograms and 100 age and sex matched control subjects without any history of symptomatic CAD. The eNOS gene intron4 b/a VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 63, 26 and 11 per cent in CAD subjects, and 72, 20 and 8 per cent in control subjects, respectively. The genotype frequencies did not differ significantly between the two groups. The frequency of the a allele was 0.24 per cent in CAD subjects and 0.18 per cent in control subjects and no significant association was found between patients and control group (P = 0.57, Odds ratio = 3.62). Plasma lipids, glucose and creatinine levels were significantly increased in CAD group. The genotypic frequencies and the allele frequency did not differ significantly between the CAD patients and controls indicating that this polymorphism was not an independent risk factor for the development of CAD in South Indian patients.     

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.     

Association of T174M polymorphism of angiotensinogen gene with essential hypertension: A meta-analysis

The association between T174M polymorphism of angiotensinogen gene and essential hypertension risk remains controversial. We herein performed a meta-analysis to achieve a reliable estimation of their relationship. All the studies published up to May 2013 on the association between T174M polymorphism and essential hypertension risk were identified by searching the electronic repositories PubMed, MEDLINE and EMBASE, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Ultimately, nine eligible studies, including 2188 essential hypertension cases and 2459 controls, were enrolled in this meta-analysis. No significant associations were found under the overall ORs for M-allele comparison (M vs. T, pooled OR 0.92, 95% CI 0.62–1.37), MM vs. TT (pooled OR 0.86, 95% CI 0.29–2.51), TM vs. TT n (pooled OR 0.91, 95% CI 0.63–1.32), recessive model (MM vs. TT+TM, pooled OR 0.89, 95% CI 0.35–2.30), dominant model (MM+TM vs. TT, pooled OR 0.91, 95% CI 0.60–1.38) between T174M polymorphism and risk for essential hypertension. This meta-analysis suggested that the T174M polymorphism of the angiotensinogen gene might not be associated with the susceptibility of essential hypertension in Asian or European populations.     

Association between interleukin 4 gene intron 3 VNTR polymorphism and recurrent aphthous stomatitis in a cohort of Turkish patients

Objective

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases, with a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. The purpose of the present study was to investigate a possible association between the functional interleukin 4 (IL4) VNTR genetic polymorphism and RAS in a sample of Turkish patients.

Methods

The study included 145 unrelated patients with a clinical diagnosis of RAS and 150 unrelated healthy controls. Genomic DNA was isolated and IL4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers.

Results

The distribution of genotype and allele frequencies of IL4 gene intron 3 VNTR polymorphism was statistically different between RAS patients and control group (p < 0.0001 and p < 0.0001, respectively) P2P2 genotype and P2 allele were also found to be protective with a lower risk for susceptibility to RAS (p < 0.0001).

Conclusion

The results of this study suggest that intron 3 VNTR polymorphism in the IL4 gene is associated with RAS susceptibility in Turkish population.     

Endothelin-1 gene and endothelial nitric oxide synthase gene polymorphisms in adolescents with juvenile and obesity-associated hypertension

Hypertension is an increasing public health problem all over the world. Essential hypertension accounts for more than 90% of cases of hypertension. It is a complex genetic, environmental and demographic trait. New method in molecular biology has been proposed a number of candidate genes, but the linkage or association with hypertension has been problematic (lack of gene-gene and gene-environment interaction). It is well known that genetic influences are more important in younger hypertensives, because children are relatively free from the common environmental factors contributing to essential hypertension. The association studies compare genotype ferquencies of the candidate gene between patient groups and the controls, in pathways known to be involved in blood pressure regulation. This study examined three polymorphisms of these factors encoding genes (ET-1 G+5665T (Lys198Asn), endothelial nitric oxide synthase (eNOS) T-786C promoter polymorphism and 27-bp repeat polymorphism in intron 4) in adolescents with juvenile essential and obesity-associated hypertension. Significant differences were found in the G/T genotype of the ET-1 polymorphism in the hypertensive and obese+hypertensive patients (body mass index (BMI) > 30). A strong association was detected between the BMI and the polymorphism of the ET-1 gene. It seems that ET-1 gene polymorphism plays a role in the development of juvenile hypertension associated with obesity. Although no significant differences were seen in the case of the eNOS promoter polymorphism and the eNOS 4th intron 27-bp repeat polymorphism. It seems that eNOS may play a role, but this is not the main factor in the control of blood pressure; it is rather a fine regulator in this process. This study with adolescents facilitates an understanding of the genetic factors promoting juvenile hypertension and obesity.     

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.     

Association between the CYP4A11 T8590C Variant and Essential Hypertension: New Data from Han Chinese and a Meta-Analysis

Objective

CYP4A11 oxidizes endogenous arachidonic acid to 20-hydroxyeicosatetraenoic acid, a renal vasoconstrictor and natriuretic in humans. Previous studies demonstrated an association between a functional variant (T8590C) of CYP4A11 and essential hypertension, though with conflicting results. To elucidate this relationship, a case-control study and meta-analysis were performed to assess the possible association of essential hypertension with CYP4A11 genetic variations.

Methods

Associations between the T8590C polymorphism and essential hypertension were examined in 328 unrelated cases and 297 age-matched controls in Han Chinese individuals. High-resolution melting was used to identify the CYP4A11 variant. To further investigate the association, we conducted a meta-analysis including eight studies published previously in July 2012.

Results

The frequency of the CYP4A11 T8590C polymorphism showed no significant difference between cases and controls (all P>0.05). However, the meta-analysis showed that the CYP4A11 T8590C polymorphism may increase the risk of essential hypertension in an additive model (OR: 1.15, 95% CI: 1.02–1.29, P = 0.02), a dominant model (OR: 1.06, 95% CI: 1.01–1.32, P = 0.03), a recessive model (OR: 1.52, 95% CI: 1.15–2.02, P = 0.003) and a homozygote contrast (OR: 1.38, 95% CI: 1.07–1.78, P = 0.01). Also, a significant relationship was observed among Caucasians in the additive model, the homozygote contrast, the recessive model and the dominant model (all P<0.05). However, no association was observed in an Asian population (all P>0.05).

Conclusions

This meta-analysis suggests there is a significant association between the CYP4A11 T8590C variant and essential hypertension, especially in Caucasians. The case-control study did not find a significant association among the Han Chinese population, but the controls were poorly matched and meaningful conclusions cannot therefore be made. Further large-scale studies are needed to clarify whether the CYP4A11 T8590C polymorphism is associated with hypertension risk in Asians or has a gender-specific effect.     

Association between polymorphisms of eNOS and GPx-1 genes, activity of free-radical processes and in-stent restenosis

Our aim was to examine correlations between polymorphisms in five antioxidant enzymes genes, activity of free-radical processes, and the risk of restenosis after coronary artery stenting with bare metal stents (BMS). A total of 101 male patients who underwent intracoronary stenting using BMS and coronary angiography follow-up of 6 months were enrolled in: group with in-stent restenosis (n = 44) and without restenosis (n = 57). The content of lipoperoxides and malondialdehyde (MDA) in Low-density lipoprotein (LDL), activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) in erythrocytes, and genotypes polymorphisms of the CAT gene (?262C/T), paraoxonase-1 (PON-1) gene (163T/A and 575A/G), endothelial nitric oxide synthase (eNOS) gene (298G/T (rs#1799983) and ?786T/C), GPx-1 gene (599C/T (rs#1050450)), and glutathione-S-transferase (GSTP) gene (313A/G) were determined. In carriers of the minor allele of 599C/T polymorphism of the GPx-1 gene, activity of GPx in erythrocytes was lower by 17 % than in wild allele homozygotes, while the content of lipoperoxides in LDL was higher by 74 %. T-allele of 599C/T polymorphism of the GPx-1 gene (OR = 2.9; 95 % CI: 1.23–6.82) and T-allele of 298G/T polymorphism of the eNOS gene (OR = 2.79; 95 % CI: 1.17–6.66) were associated with the risk of in-stent restenosis. Minor alleles of polymorphisms 298G/T of the eNOS gene and 599C/T of the GPx-1 gene are associated with an increased risk of in-stent restenosis. Minor allele of the GPx-1 gene 599C/T polymorphism leads to a decrease of the GPx activity and increase of the activity of free-radical processes.