Effects of the T-786C,G894T,and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene on the risk of prostate cancer

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 ± 12.4 years) and 340 age-matched healthy controls (mean age 64.9 ± 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) = 3.62, 95% confidence interval (CI): 1.89–7.74, P = 0.002), high grade tumor (OR = 2.46, 95% CI:1.78–4.72; P = 0.006), and advanced disease (OR = 4.67, 95% CI: 2.64?8.61; P = 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b “a” variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR = 2.12, 95% CI: 1.68–3.44; P = 0.031 for 4a/b ab genotype, and OR = 4.32, 95% CI: 2.21–6.08; P = 0.001 for 4a/b aa genotype). In addition, genotypes with the “a” allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR = 4.76, 95% CI: 2.74–8.62; P = 0.001) and advanced CaP (OR = 5.28, 95% CI: 3.64–8.72; P = 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR = 0.44, 95% CI: 0.33–0.77; P = 0.004, and OR = 0.39, 95% CI: 0.26–0.61; P = 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.     

冠心病与内皮型一氧化氮合酶基因多态性的关系

目的 探讨内皮型一氧化氮合酶(eNOS)基因-786T/C,4a4b,894G/T等3个多态性位点与冠心病(CAD)发病相关.方法 对146例中国汉族人群CAD患者和113例正常对照进行遗传学分析,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和PCR技术分析2个SNP位点即-786T/C和894G/T,以及1个VNTR位点4a4b,检测各位点基因型和等位基因频率,采用HaploView 4.0及SPSS 13.0软件经x2检验比较两组间各位点基因型及等位基因频率的差异.结果 CAD组中eNOS基因-786T/C位点CC基因型频率为2.0%,4a4b位点4a/4a基因型频率为5.4%,对照组eNOS基因-786T/C位点CC基因型频率为0.0%,4a4b位点4a/4a基因型频率为0.9%,差异有统计学意义(P＜0.05).CAD组和对照组在eNOS基因的894G/T位点等位基因和基因型频率分布差异均无统计学意义(P＞0.05).结论 eNOS基因-786T/C和4a4b多态性与中国汉族人群CAD存在关联,C等位基因和4a等位基因可能是CAD发病的危险因素.eNOS基因894G/T位点与CAD发病无明显相关.

Abstract：

Objective To investigate the relationship between the 3 polymorphisms ( -786T/C,4a4b,894G/T) in endothelial nitric oxide synthase (eNOS) gene and coronary artery disease (CAD).Methods 146 patients with CAD and 113 healthy unrelated individuals in a Chinese Han nation were involved.The genotype and allele frequency of each polymorphism of the eNOS gene in these patients and normal controls were examined by using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or PCR methods.Genotypes and allele frequency were analyzed by HaploView 4.0 and SPSS13.0 software.Results The frequency of CC genotype of the -786T/C was 2.0%,and that of 4a/4a genotype of the 4a4b was 5.4% in CAD.The frequency of CC genotype of the - 786T/C was 0.0%,and that of 4a/4a genotype of the 4a4b was 0.9% in controls ( P＜0.05 ).There were significant differences in both allele and genotype frequency of -786T/C and 4a4b between CDA group and control group.Between patients with CAD and controls,there were no significant differences in the frequency of the genotypes and alleles of the 894G/T in eNOS gene.Conclusion The - 786T/C and 4a4b polymorphisms of eNOS gene may be associated with CAD.The individuals with C allele of - 786T/C and 4a allele of 4a4b are susceptible to CAD.There is no significant correlation between 894G/T polymorphism in eNOS gene and CAD.     

eNOS G894T polymorphism as a mild predisposing factor for abdominal aortic aneurysm

OBJECTIVE: Abdominal aortic aneurysm (AAA) represents a chronic degenerative condition associated with atherosclerosis. Actually, data from experimental and clinical studies suggest that nitric oxide (NO) is a modulator in maintaining endothelial function and antithrombotic intravascular environment. Reduced vascular NO generation in subjects carrying the rare variants of the eNOS gene might predispose to AAA. No information is available about the influence of the eNOS gene T-786C, G894T, and 4a/4b polymorphisms in the susceptibility to the disease. METHODS: In this study, we evaluated the role of these polymorphisms in the predisposition to AAA and their influence in hypertensive and normotensive patients. We studied 250 consecutive patients with AAA referred to the Unit of Vascular Surgery of the University of Florence compared with 250 truly healthy subjects with a negative history of vascular diseases. All subjects, patients, and controls, underwent duplex scanning examination, and to assess the presence of other atherosclerotic localizations, all patients underwent clinical and instrumental examinations. RESULTS: A significant difference in genotype distribution and allele frequency was observed for eNOS G894T but not for T-786C and 4a/4b polymorphisms. At the multivariate analysis after adjustment for traditional vascular risk factors and other atherosclerotic localizations, the eNOS 894T variant was significantly associated with AAA, according to dominant and recessive models (dominant model odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.21-3.93, P = .007; recessive model OR: 2.7, 95% CI: 1.42-5.20, P = .002). When patients with other atherosclerotic localizations were excluded from the analysis, the 894T variant still remained associated with the predisposition to AAA, according to the models considered (dominant model OR: 2.1, 95%CI: 1.23-3.92, P = .007; recessive model OR: 2.8, 95%CI: 1.45-5.24, P = .002). CONCLUSIONS: The present study showed that the eNOS G894T polymorphism is a mild modulator of the predisposition to AAA apart from traditional risk factors, suggesting a genetic influence on the molecular mechanisms responsible for this complex disease.     

Association of the T-786C, G894T and 4a/4b polymorphisms of the endothelial nitric oxide synthase gene with vasculogenic erectile dysfunction in Iranian subjects

What's known on the subject? and What does the study add? We know that nitric oxide (NO) plays a significant role in penile tumescence. NO is produced during enzymatic conversion of L‐arginine to L‐citrulline by three distinct isoforms of NO synthase (NOS), namely, inducible (iNOS), endothelial (eNOS) and neural (nNOS). The endothelial isoform of NOS (eNOS), encoded by the NOS3 gene, is the main source of NO. We determined all three eNOS gene polymorphisms in men with vasculogenic erectile dysfunction. There was a significant difference between the group of men with vasculogenic erectile dysfunction and normal healthy men when compared by genotype distribution.

OBJECTIVE

? To investigate the association of the T‐786C, G894T and variable number of tandem repeats (VNTRs) in intron 4 (a/b) polymorphisms of the eNOS gene in Iranian subjects with vasculogenic erectile dysfunction (ED).

PATIENTS AND METHODS

? A total of 322 consecutive patients with vasculogenic ED were recruited. Patients with concomitant risk factors for ED were excluded. ? Patients with ED were identified based on history‐taking, detailed physical examination, serum biochemistry, sex hormone measurements, application of the International Index of Erectile Function (IIEF) questionnaire, and penile duplex Doppler ultrasonography after intracavernosal injection of 20 µg prostaglandin E₁. The control group comprised 318 age‐matched healthy male volunteers. ? Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism and the T‐786C, G894T and VNTR intron 4 polymorphisms of the eNOS gene were determined.

RESULTS

? After multivariate regression analysis, significant differences were seen in the frequencies of genotypes and alleles of the two T‐786C and G894T polymorphisms when patients with ED and normal controls were compared. ? In a multiple logistic regression analysis, the odds ratio (OR) of increased ED was strongly associated with the ‐786C allele [adjusted OR = 3.12, 95% confidence interval (CI) = 2.28–4.25; P= 0.001] and the 894T allele (adjusted OR = 3.87, 95% CI = 2.53–4.87; P= 0.001). ? The data showed a higher prevalence of the T‐786C CC genotype (adjusted OR = 2.72, 95% CI = 1.88–3.65; P= 0.006), and the G894T GT (adjusted OR = 1.72, 95% CI 1.24–2.83; P= 0.037) and G894T TT genotypes (adjusted OR = 3.42, 95% CI 2.42–4.26; P= 0.001) in patients with ED than in the controls.

CONCLUSIONS

? The findings of the present study suggest that the eNOS T‐786C and G894T polymorphisms are strong predictors of the predisposition to ED in addition to traditional risk factors, signifying a genetic influence for this multifactorial disease. ? Further studies in different ethnic populations are needed to better elucidate the role of eNOS gene polymorphism in the pathogenesis of ED.     

Relation of nitric oxide synthase gene (NOS3) polymorphisms to varicocele risk and post-varicocelectomy seminal oxidative stress reduction

The pathophysiology of varicocele remains to be unknown. Several genetic factors have been implicated in varicocele etiopathogenesis. We studied the relationship between NOS3 c.894G>T, c.786T>C and 4b/a polymorphisms to varicocele risk and their prognostic value as regards improvement of the post-operative seminal parameters &/or seminal malonaldehyde levels. The three NOS3 polymorphisms were evaluated in 100 patients with varicocele and 100 healthy subjects by RT-PCR. Seminal plasma MDA level was measured pre-operatively and 3 months after varicocelectomy by the thiobarbituric acid method. The GT, TT, TC and bb genotypes of NOS3 polymorphism were more commonly observed in varicocele patients (30%, 9%, 28% and 70% respectively) compared to normal controls (12%, 0%, 10% and 50% respectively). The mean percentage of post-varicocelectomy seminal MDA reduction was highest with the GT genotype (p < .001). Genotypes GT+TT, TC and bb were associated with varicocele occurrence in our patients. The T (c.894G>T), C (c.786T>C) and b (NOS3 intron 4 VNTR) alleles were significantly associated with varicocele occurrence in our cohort of patients. We also report a better response regarding the reduction of seminal MDA after varicocelectomy with the GT and ba genotypes.     

Endothelial nitric oxide synthase gene/gender interactions and the renal hemodynamic response to angiotensin II

Endothelial function is dependent on the generation of nitric oxide (NO) by the enzyme endothelial NO synthase (eNOS). One functional coding polymorphism of the eNOS gene (G894-->T) is associated with reduced enzyme activity, increased coronary heart disease, and the development of end-stage renal failure. Because gender and renin-angiotensin system activation also play key roles in the development of renal and cardiovascular disease and because NO plays a role in the response to angiotensin II (AngII), it was hypothesized that the eNOS gene G894-->T polymorphism would be a determinant of the systemic and renal vascular response to AngII. Fifty young, healthy, normotensive individuals who were on a controlled sodium and protein diet for 1 wk underwent assessment of BP and renal hemodynamic function at baseline and during AngII infusion (4 ng/kg per min for 45 min). Participants were genotyped for the eNOS gene G894-->T polymorphism and then segregated into groups on the basis of gender and genotype (GG versus GT/TT). Baseline values for renal blood flow, effective renal plasma flow, and GFR were lower in men with the T allele compared with men who were homozygous for the G allele (P = 0.03), but the polymorphism was not associated with renal hemodynamic function in women. The BP responses to AngII were similar in men and women regardless of genotype. Both multivariate linear regression and analysis of covariance (ANCOVA) revealed a relationship between gender and genotype. Men with the GT/TT genotype exhibited a significantly greater decrease in GFR (P = 0.04) in response to AngII than did those with the GG genotype. This association was not observed in women. The eNOS gene G894-->T polymorphism is a determinant of both baseline renal hemodynamic function and the hemodynamic response to AngII in men but not in women.     

MicroRNA-34b/c rs4938723 T>C多态性与中国汉族人群肾细胞癌易感性的相关性

目的研究中国汉族人群microRNA-34b/c启动子区TC(rs4938723)多态性与肾细胞癌易感性之间的关系。方法采用病例对照研究模式,通过TaqMan探针PCR法检测年龄和性别匹配的710例中国汉族人群肾细胞癌患者和760例正常人群的microRNA-34b/c启动子区TC(rs4938723)基因型,探讨该位点基因多态性与肾细胞癌易感性之间的关系。结果与TT/TC基因型携带者相比,CC型(OR=1.53,95%CI=1.06~2.21,CC基因型比TT基因型;OR=1.48,95%CI=1.05~2.10,CC基因型比TT/TC基因型)携带者发生肾细胞癌的危险性明显升高。分层分析显示携带CC基因型的老年患者(OR=1.80,95%CI=1.08~3.01)、男性患者(OR=1.64,95%CI=1.08~2.51)、吸烟患者(OR=2.07,95%CI=1.16~3.69)及饮酒患者(OR=1.94,95%CI=1.01~3.73)发生肾细胞癌的危险性明显升高。结论 microRNA-34b/c启动子区TC(rs4938723)基因多态性与我国汉族人群肾细胞癌易感性有关,CC型携带者发生肾细胞癌的危险性要明显高于TT/TC型携带者。     

eNOS gene T786C,G894T and 4a4b polymorphisms and male infertility susceptibility: a meta‐analysis

The association between polymorphism of eNOS and male infertility in several studies was controversial. To explore a more precise estimation of the association, a meta‐analysis of eight case–control studies, including 1,968 cases and 1,539 controls, were selected. The meta‐analysis was conducted by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Overall, the association between T786C and risk of male infertility was obvious (TC vs. TT: OR, 1.20; 95% CI, 1.01–1.42; CC vs. TT: OR, 3.37; 95% CI, 1.65–6.87; TC/CC vs. TT: OR, 1.47; 95% CI, 1.25–1.73; CC vs. TT/TC: OR, 3.18; 95% CI, 1.54–6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27–2.03). However, no overall association was observed between the other two polymorphisms of eNOS (G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility.     

Association of endothelial nitric oxide synthase gene polymorphisms with end-stage renal disease: a systematic review and meta-analysis

Background and objective: Endothelial nitric oxide synthase (eNOS) is one of the potent regulators of intra renal hemodynamics. Polymorphisms of eNOS gene may be involved in the progression of renal disease, and may be the causative factors that contribute to the deterioration of renal functions. During the past decades, several studies investigated the association of eNOS polymorphisms with the risk of end-stage renal disease (ESRD), but the results remain unclear and the mechanisms are not defined. Our study was designed to examine the role of different eNOS genetic polymorphisms in the progression of ESRD. Materials and methods: Relevant studies were identified through PubMed, Embase, Medline and CNKI (China National Knowledge Infrastructure) database published between January 2000 and November 2013. The association between eNOS polymorphisms and ESRD susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CI) in fixed or random effects models. Results: Sixteen articles were identified for the analysis of association between eNOS gene polymorphisms and ESRD risk. A total of 2729 patients and 2190 controls for 4b/a, 851 patients and 1171 controls for G894T, and 513 patients and 487 controls for T786C were included in our analysis. Overall, 4a allele of 4b/a polymorphism produced a significant association in the global population (OR?=?1.47, 95% CI?=?1.05–2.06, p?=?0.03) in a random-effect model; T allele of G894T was also significantly associated with ESRD susceptibility in overall populations (OR?=?2.12, 95% CI?=?1.44–3.12, p?=?0.0001). Furthermore, 4a and T carriers were significantly associated with ESRD risk as well. No association was found between T786C polymorphism and ESRD. Conclusion: The evidence accumulated suggested that 4b/a and G894T polymorphisms in the eNOS gene were associated with ESRD susceptibility, indicating that 4a and T allele carriers might become significant genetic molecular markers for the onset of ESRD in overall populations. However, more studies should be performed in the further studies.     

生长分化因子5 rs143383基因多态性与膝关节骨关节炎相关性的Meta分析

目的探究生长分化因子5（GDF5）rs143383基因多态性与膝关节骨性关节炎发生的相关性。 方法检索建库至2022年1月1日已经发表的关于GDF5 rs143383基因多态性与膝关节骨性关节炎之间相关性的文献,检索数据库包括PubMed、Embase、Web of Science、中国知网、万方和维普数据库等。依据检索策略检索,16篇文献（17项数据）符合纳入排除标准,从所需研究中提取数据后,确定优势比（OR）及其95%置信区间（CI）以评估。通过漏斗图评估发表偏差。 结果GDF5（rs143383）基因多态性与膝关节骨性关节炎发生之间具有明显相关性。在总体的等位基因模型（T vs C：OR=1.20,95% CI：1.14,1.26,P<0.01）、共显基因模型（TT vs CC：OR=1.45,95% CI：1.30,1.62,P<0.01）和显性基因模型（TT+TC vs CC：OR=1.29,95%CI：1.17, 1.43,P<0.01）,均提示GDF5基因多态性与膝关节骨性关节炎的发生有明显相关性。此外,我们还根据种族进行亚组分型,通过亚组分析在亚洲人群以及高加索人群的等位基因模型（亚洲人群：T vs C：OR=1.22,95% CI：1.13,1.30,P<0.01;高加索人群：T vs C：OR=1.18,95% CI：1.10,1.26,P<0.01）、共显基因模型（亚洲人群：TT vs CC：OR=1.58,95% CI：1.33,1.88,P<0.01;高加索人群：TT vs CC：OR=1.37,95% CI：1.19,1.59,P<0.01）和显性基因模型（亚洲人群：TT+TC vs CC：OR=1.40,95% CI：1.18,1.65,P<0.01;高加索人群：TT+TC vs CC：OR=1.24,95% CI：1.08,1.42,P<0.01）中均观察到了GDF5 rs143383基因多态性与膝关节骨性关节炎发生显著的关联,然而在非洲人群中无明显关联。 结论GDF5 rs143383基因多态性与膝关节骨性关节炎发生具有显著联系,尤其在亚洲人群和高加索人群中具有相关性。     

Associations between endothelial nitric oxide synthase polymorphisms and risk of diabetic nephropathy: an updated meta-analysis

Abstract

Background: Genetic polymorphism of endothelial nitric oxide synthase (eNOS) has been implicated in the risk of diabetic nephropathy (DN), but the published findings were inconsistent. We performed a comprehensive meta-analysis to derive a more precise estimation of the association between genetic polymorphisms of eNOS and the risk of DN. Methods: Six online database were researched on the associations between polymorphisms of eNOS (T786C, G894T, 4b/4a) and DN risk. PRISMA statement and Hardy–Weinberg equilibrium assessment were used in this report. Odds ratio and 95% confidence interval were estimated based on the following genetic contrast/models: allelic model, dominant model, recessive model and co-dominant model. The publication bias and sensitivity analysis were also performed to guarantee the statistical power. Results: A total of 49 case–control studies with 11,990/9754/5131 participants for DN/DM/HC group were eligible for meta-analysis (7/25/31 studies for T786C/G984T/4b/a). For the eNOS-T786C, C allele showed a weak association between C allele and DN risk in DN/T2DM group. For eNOS-G894T, there was an association between T allele and DN risk in the global, Asian and African population in DN/T2DM group. For the eNOS-4b/4a, 4a allele was found contributing significantly to increased DN risk in the global population. Conclusion: Our comprehensive meta-analysis suggests that three polymorphisms of eNOS may be the increased risk factors of DN development, especially in Asian population and T2DM group.     

The associations among eNOS G894T gene polymorphism, erectile dysfunction and related risk factors

OBJECTIVE: To investigate the possible correlations among eNOS G894T polymorphism, erectile dysfunction (ED) and related risk factors in a Taiwanese population. MATERIALS AND METHODS: In all, 151 patients with ED and 77 healthy controls were enrolled. All the men had a complete clinical history taken and laboratory data was collected. To assess erectile conditions the five-item version of the International Index of Erectile Function (IIEF-5) was used. The eNOS G894T polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: In all, 228 men were enrolled with a mean (sd) age of 58.6 (9.7) years. In a univariate analysis, age, serum testosterone level, and the prevalence of diabetes mellitus (DM) and hypertension were significantly different between patients with ED and the healthy controls (P < 0.01). In the multiple logistic regression analysis, DM, age and hypogonadism were three independent risk factors for ED (P = 0.018, P = 0.046 and P = 0.016, respectively). The prevalence of ED in T allele carriers (GT/TT) was significantly greater than in G allele carriers (GG; 80.0% vs 63.3%, P = 0.04). Also the eNOS 894T allele carriers had significantly lower IIEF-5 scores than the eNOS 894G allele carriers, at 13.2 (5.3) vs 15.7 (6.1) (P = 0.01) and it was associated with increment of T allele number (11.0 (5.6) vs 13.6 (5.2) vs 15.7 (6.1); P = 0.03). CONCLUSION: Our results indicate that DM, age and hypoganadism are three significant independent risk factors for ED. Also, in the Taiwanese population, the eNOS 894T allele carriers are at greater risk of ED, both in prevalence and severity, and this might be a factor of genetic susceptibility.     

Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size

OBJECT: Among patients with aneurysms, those with heterozygous (T/C) endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), a mutation reducing endothelial nitric oxide synthesis, are reported to have larger ruptured intracranial aneurysms (IAs) than those with homozygous (C/C or T/T) genotype. The authors tested patients harboring aneurysms for eNOS T-786C SNP in two populations--Japanese and Korean. METHODS: The eNOS T-786C SNP was genotyped through direct sequencing in genomic DNA obtained from 336 Japanese and 191 Korean patients with lAs and 214 Japanese and 191 Korean control volunteers. Differences in genotype frequencies among the various aneurysm sizes were evaluated using the Fisher exact test. There was no significant difference in heterozygous (T/C) eNOS T-786C SNP between aneurysms 5 mm or smaller and those from 6 to 9 mm, and between lesions 5 mm or smaller and those 10 mm or larger in 336 Japanese patients harboring aneurysms--220 with ruptured and 116 with unruptured lesions--and in 191 Korean patients with ruptured aneurysms. CONCLUSION: The eNOS T-786C SNP genotype does not influence the size of aneurysms.     

Glu298Asp endothelial nitric oxide synthase polymorphism is a risk factor for erectile dysfunction in the Mexican Mestizo population

Penile erection depends on the balanced action between antagonist vasoactive molecules such as nitric oxide (NO) and angiotensin. Endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) polymorphisms have been associated with endothelial dysfunction, which is described as a cause of erectile dysfunction (ED). Endothelial NOS and ACE are both regulators of vascular and corporal smooth muscle tone, which are connected by interaction between the NO-cyclic guanosine monophosphate pathway and the renin-angiotensin system. We analyzed the frequencies of 894 G/T (Glu298Asp) eNOS and ACE I/D polymorphisms in Mexican patients with ED (n=53) and in an age-matched control group (n=62). The populations analyzed were in Hardy Weinberg equilibrium. We found significant differences in allelic (chi2=4.42; P=.03) and genotypic frequencies (chi2=3.96; P=.04) between patients and controls for the 894 G/T eNOS polymorphism. Presence of the 894T allele in carriers increased the risk of ED (odds ratio [TT + GT versus GG] = 2.37; 95% confidence interval, 1.08 to 5.21; P=.02). Multiple logistic regression analysis showed that the Glu298Asp polymorphism was an independent factor for ED, as was diabetes mellitus, hypertension, cardiac disease, and cigarette smoking. No association was found between ACE I/D polymorphism and ED in the population studied. Therefore, our results suggest that Glu298Asp eNOS polymorphism plays a role as a genetic susceptibility factor for ED.     

CD14基因启动子区-159位点多态性在重度烧伤患者中的分布及意义

目的 了解CD14基因启动子-159C/T基因多态性与严重烧伤患者CD14 mRNA表达及血浆可溶性CD14(sCD14)水平的关系.方法 2004年6月-2006年6月,选择2个笔者单位收治的烧伤总面积大于或等于30%TBSA的患者77例,分别于伤后1、3、5、7、14、21、28 d抽取患者静脉血,采用PCR-限制性片段长度多态性法检测血浆CD14-159C/T基因多态性,酶联免疫吸附测定法、RT-PCR法检测患者血浆sCD14的含量及白细胞CD14 mRNA表达.结果 77例患者的CD14基因C-159T基因型中,CC纯合子型7例占9.1%、TC杂合子型49例占63.6%、TT等位基因纯合子型21例占27.3%,T等位基因和C等位基因分布频率分别为59.1%和40.9%.经检验表明,此研究群体达到了Hard-Weinberg平衡.7例CC纯合子型患者中并发脓毒症3例占42.9%,49例TC杂合子型并发该症38例占77.6%,21例TT等位基因纯合子型并发该症15例占71.4%.3例CC纯合子型脓毒症患者中,1例出现MODS;38例TC杂合子型脓毒症患者19例出现MODS占50.0%;15例TT等位基因纯合子型脓毒症患者10例出现MODS占66.7%.伤后7～21 d TC杂合子型、TT等位基因纯合子型患者外周血CD14 mRNA表达明显高于CC纯合子型患者(P＜0.05或P＜0.01).伤后7d TC杂合子型、TT等位基因纯合子型患者CD14 mRNA表达达高峰,分别为1.18±0.25、1.15±0.35.烧伤后TC杂合子型、TT等位基因纯合子型患者血浆中sCD14含量较高,伤后5 d CC纯合子型患者血浆sCD14含量(85±46)μg/L显著低于TC杂合子型患者[(134±43)μg/L,P＜0.01];伤后21、28 d TC杂合子型、TT等位基因纯合子型患者sCD14含量明显高于CC纯合子型患者(P＜0.01).结论 大面积烧伤后CD14基因启动子-159位点多态性TT基因型可能是烧伤感染患者发生MODS的主要基因标志物之一.携带TT基因型的烧伤脓毒症患者并发MODS概率高于其他基因型.     

Analysis of endothelial nitric oxide synthase (eNOS) G894T polymorphism and semen parameters in a Chinese Han population

Previous studies have shown that endothelial nitric oxide synthase (eNOS) gene may be involved in abnormal semen parameters. However, the relationship between eNOS G894T polymorphism and semen parameters remains controversial. The purpose of this study was to investigate the association of eNOS G894T polymorphism and semen parameters. The genotype frequency of eNOS G894T was determined in 270 idiopathic asthenozoospermia patients and 248 ethnically matched healthy volunteers using iPLEX genotyping assays on a MassARRAY^® (Sequenom, San Diego, CA, USA) platform. The statistical analysis performed with Fisher's exact test showed no significant difference in frequencies of genotypes between both groups. The logistic regression showed that genotypes GT, TT and allele T were nonassociated with increased risk of asthenozoospermia in the patient group with ≤5% or >5% sperm with normal forms. The dependence on genotypes of semen parameters was further investigated in both patients and control group. There was no significant difference as compared to control group (P > 0.05). Our study indicated that eNOS gene G894T polymorphism may not have an adverse effect on semen parameters in a Chinese Han population.     

血管内皮生长因子936C／T基因多态性与结直肠腺瘤易感性的关系

目的探讨血管内皮生长因子（VEGF）1498C／T、936C／T基因多态性与结直肠腺瘤易感性的关系。方法对224份结直肠腺瘤及200份正常对照标本进行研究．应用TaqMa。探针法检测VEGF1498C／T、936C／T基因型,搜集相对应的临床病理资料。结果与VEGF936CC基因型相比．CT基因型和CT＋TT基因型患者结直肠腺瘤的发生危险显著增加（DR=2．00,95％CI：1．23—3．25,P=0．006;OR=2．04,95％C1：1．28—3．26,P=0．003）;与VEGF936-C等位基因相比,T等位基因携带者结直肠腺瘤的发生危险亦显著增加（DR=1．91,95％CI：1．25—2．91．P=0．003）。结直肠腺瘤患者为VEGF936CT＋TT基因型或携带T等位基因,其病理类型倾向于绒毛状腺瘤（OR=2．54,95％CI：1．12—5．75,P：0．040;OR=3．08,95％CI：1．64-5．80,P=0．001）。VEGF1498C／T基因多态性在腺瘤组与对照组间的差异无统计学意义（19〉0．05）。结论VEGF936C／T基凶多态性与结直肠腺瘤易感性密切相关。     

Association of transforming growth factor beta1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis.

Transforming growth factor beta (TGF-beta) is an important regulator of bone metabolism, its effects being intertwined with those of estrogen and vitamin D. A T-->C polymorphism in exon 1 of the TGF-beta1 gene, which results in the substitution of proline for leucine, is associated with bone mineral density (BMD). However, it is not known whether this polymorphism affects the response to treatment with active vitamin D or to hormone replacement therapy (HRT) in individuals with osteoporosis. Changes in BMD at the lumbar spine (L2-L4 BMD) were compared among TGF-beta1 genotypes in 363 postmenopausal Japanese women who were divided into three groups: an untreated, control group (n = 130), an active vitamin D treatment group (n = 117), and an HRT group (n = 116). TGF-beta1 genotype was determined with an allele-specific polymerase chain reaction assay. In the control group, the rate of bone loss decreased according to the rank order of genotypes TT (homozygous for the T allele) > TC (heterozygous) > CC (homozygous for the C allele), with a significant difference detected between the CC and TT genotypes. The positive response of L2-L4 BMD to HRT increased according to the rank order of genotypes TT < TC < CC, although the differences among genotypes were not statistically significant. Individuals with the CC genotype responded to active vitamin D treatment with an annual increase in L2-L4 BMD of 1.6%, whereas those with the TT or TC genotypes similarly treated lost bone to a similar extent as did untreated subjects of the corresponding genotype. These results suggest that TGF-beta1 genotype is associated with both the rate of bone loss and the response to active vitamin D treatment.     

Association between decreased kidney function and endotoxin receptor CD14 C-159T polymorphism among Japanese health check-up examinees

BACKGROUND: A recently identified promoter polymorphism of the endotoxin receptor (CD14 C-159T) was shown to be associated with atherosclerotic diseases such as myocardial infarction. This study was conducted to determine whether this polymorphism is associated with decreased kidney function. METHODS: A total of 281 male and 522 female health check-up examinees, aged 39-88 years, were genotyped for CD14 C-159T. The glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease (MDRD) Study equation. Estimated GFR (eGFR) and the proportion of subjects with mildly decreased eGFR (eGFR under 90 mL/min/1.73 m(2)) were compared among the genotypes. RESULTS: Subjects carrying the T allele showed decreased age- and sex-adjusted eGFR compared with those with CC genotype (101+/-22 vs. 105+/-23 mL/min/1.73 m(2); mean+/-SD, p = 0.012). The proportion of subjects with mildly decreased eGFR was higher in T allele carriers (34.2% for TT+CT and 26.3% for CC genotype, p = 0.041), but not statistically significant when adjusted for age and sex (odds ratio [OR] 1.41, 95% CI 0.97-2.05, p = 0.076). In subjects under 65 years, T allele carriers had a significantly increased risk for mildly decreased eGFR (27.1% for TT+CT and 18.0% for CC; age- and sex-adjusted OR 1.82, 95% CI 1.06-3.12, p = 0.030). CONCLUSION: CD14-159T allele was associated with decreased eGFR compared with CC genotype, and with a higher prevalence of mildly decreased eGFR in younger subjects under 65.