内皮源一氧化氮合酶基因单核苷酸多态性与高血压病相关性研究

目的分析一氧化氮合酶基因NOS3 A-922 G、NOS3 T-786C与NOS3 G894T单核苷酸多态性(SNP)的等位基因频率分布与高血压病的相关性。方法选择无血缘关系的高血压病患者192例(高血压病组)及正常健康人122例(对照组),获取其静脉血白细胞基因组DNA。采用等位基因特异性引物聚合酶链反应技术检测NOS3NOS3 A-922G、NOS3 T-786C与NOS3 G894T 3个位点的基因型。结果高血压病组NOS3 G894T、NOS3A-922G和NOS3 T-786 C各相应的等位基因型分布频率和等位基因单倍型频率与对照组比较无显著性差异(P>0.05)。两组按男女性别分层研究,男女人群亦未发现NOS3 A-922 G、NOS3 T-786C与NOS3 G894T各个位点单核苷酸多态性与高血压病有相关性。结论我们的研究未能发现人群中NOS3A-922 G、NOS3 T-786C与NOS3 G894T SNP与其高血压病有明确的相关性,且无性别差异。     

NOS2 C-1173T、G-954C单核苷酸双重多态性与高血压病的关系

目的研究中国汉族人群诱导型一氧化氮合酶(NOS2)基因启动子区C-1173T、G-954C单核苷酸双重多态性(SNP)及其基因型组合与高血压病的相关性.方法随机选择的高血压病个体192人(男97例,女95例)以及健康汉族个体109例(男61例,女48例)检测血白细胞基因DNA,利用嵌巢式等位基因特异性引物PCR技术检测NOS2 C-1173 T(C-T)、NOS2 G-954C SNP(G-C),并应用聚类分析其基因多态性特征.结果 NOS2 C-T与G-CSNP基因型分布高血压病组CC基因型频率(64.06%)与正常对照组(59.17%)相比无差异(P>0.05),TT基因型频率较正常对照组低(P<0.05,χ24.804).在女性高血压病患者T等位基因频率与正常对照组无显著性差异;而在男性高血压病患者T等位基因频率较正常对照组低(P<0.05,χ25.182).NOS2 C-T与G-C 组合基因型分布发现高血压病组携带TT+GG与TT+GC总频率明显低于正常对照组(P<0.05,χ24.804),男性高血压病患者尤为明显(P<0.05,χ24.2876).结论 (1)中国汉族人群NOS2 C-1173 T 多态性与男性患高血压病有相关性;NOS2 G-954C SNP多态性与高血压病无关.(2)在高血压病男性病人携带 T-1173T+NOS2 G-954G与NOS2 T-1173T+NOS2 G-954C频率较正常对照组低.     

蒙族高血压患者内皮型一氧化氮合酶(eNOS)基因多态性研究

目的旨在探讨一氧化氮合酶(eNOS)基因(G894T、T786C)多态性与中国蒙古族高血压患者的相关性。方法采用聚合酶链反应和限制性酶切的片段长度多态分析方法检测蒙族高血压患者100例和健康人50例的一氧化氮合酶(eNOS)基因(G894T、T786C)多态性。结果一氧化氮合酶基因T894G(GT、TT)、T786C(CT、CC)基因型及T、C等位基因频率在高血压组显著高于对照组(P <0．05)。同时具有eNOS894TT、786CC和894TG、786TC基因型者高血压组比对照组多,差异有显著性(P<0．05)。结论一氧化氮合酶基因T894G、T786C基因多态性与蒙族高血压相关,但尚需在更大的人群中进一步验证。     

重庆地区汉族老年人群klotho G-395A、F352V与C370S基因多态性及其组合分布

目的 研究重庆地区汉族老年人群klotho G-395A、F352V与C370S 3个位点的单核苷酸多态性(SNP)及其等位基因频率、单倍型组合分布特征.方法 利用单一等位基因特异性引物PCR技术检测klotho G-395A、F352V、C370S的SNP,应用聚类分析其基因多态性特征.结果 klotho G-395A SNP 基因型分布 GG、GA、AA分别为47.66%、42.58%、9.76%,G、A等位基因频率分别为68.95%、31.05%;klotho F352V SNP 基因型分布 FF、FV、VV分别为35.49%、59.09%、5.61%,F、V等位基因频率分别为65.04%、34.96%;klotho C370S SNP 基因型分布CC CS、SS分别为37.30%、58.76%、3.88%,C、S等位基因频率分别为66.68%、33.32%.研究发现了klotho基因在3个位点的SNP前10种组合基因型分布:klotho G-395G+F352V+C370S 253例(16.92%),klotho G-395A+F352V+C370S 241例(16.12%),klotho G-395G+F352V+C370C 152例(10.17%),klotho G-395A+F352V+C370C 131例(8.76%),klotho G-395G+F352F+C370S 126例(8.43%),klotho G-395A+F352F+C370C 121例(8.09%),klotho G-395G+F352F+C370C 109例(7.29%),klotho G-395A+F352F+C370C 86例(5.75%),klotho A-395A+F352V+C370S 52例(3.48%),klotho A-395A+F352F+C370C 30例(2.01%),klotho G-395G+V352V+C370S 30例(2.01%).结论 本研究首次揭示了klotho基因的3个位点的SNP基因型组合分布特征,为进一步开展klotho基因及其表达研究提供了线索和依据.     

高血压病患者G蛋白β3基因C825T和eNOS基因G894T多态性研究

目的　观察高血压病 (EH)患者G蛋白 β3亚单位基因 (GNB3)C82 5T多态性和内皮一氧化氮合酶 (eNOS)基因G894T多态性 ,探讨EH发生的遗传学机制。方法　EH患者 112例 ,对照组 112例。取血标本提取DNA ,用PCR方法扩增目的基因 ,用限制性内切酶 (BanⅡ、BseDI)酶切PCR产物用于基因分型。结果　EH患者GNB3C82 5T基因型分布 (基因型频率CC =0 34,CT =0 5 3 ,TT =0 13)与对照组有显著性差异 (基因型频率CC =0 5 9,CT =0 36 ,TT =0 0 5。χ2 =6 9,P <0 0 5 ) ;82 5T等位基因携带者与CC纯合子比较有较高的患EH的危险 (OR =2 2 ,95 %CI1 1～ 4 6 )。eNOS各基因型在EH的分布与对照组无显著性差异。Logistic回归分析显示 ,GNB3 82 5T等位基因与EH关联最密切。结论GNB3基因C82 5T多态性的 82 5T等位基因是EH发病的遗传危险因子。eNOS基因G894T多态性在EH发病中不起直接重要作用。     

NOS2 C-1173T、G-954C单核苷酸双重多态性与高血压病的关系

目的研究中国汉族人群诱导型一氧化氮合酶(NOS2)基因启动子区C-1173T、G-954C单核苷酸双重多态性(SNP)及其基因型组合与高血压病的相关性。方法随机选择的高血压病个体192人(男97例,女95例)以及健康汉族个体109例(男61例,女48例)检测血白细胞基因DNA,利用嵌巢式等位基因特异性引物PCR技术检测NOS2C-1173T(C-T)、NOS2G-954CSNP(G-C),并应用聚类分析其基冈多态性特征。结果NOS2C-T与G-CSNP基因型分布:高血压病组CC基因型频率(64.06％)与正常对照组(59.17％)相比无差异(P>0.05),TT基因型频率较正常对照组低(P<0.05,x2=4.804)。在女性高血压病患者T等位基因频率与正常对照组无显著性差异;而在男性高血压病患者T等位基因频率较正常对照组低(P<0.05,x2=5.182)。NOS2C-T与G-C组合基因型分布发现:高血压病组携带TT+GG与TT+GC总频率明显低于正常对照组(P<0.05,x2=4.804),男性高血压病患者尤为明显(P<0.05,x2=4.2876)。结论(1)中国汉族人群NOS2C-1173T多态性与男性患高血压病有相关性;NOS2G-954CSNP多态性与高血压病无关。(2)在高血压病男性病人携带,T-1173T+NOS2G-954G与NOS2T-1173T+NOS2G-954C频率较正常对照组低。     

2型糖尿病病人NOS3基因多态性与冠心病发病风险的倾向性评分匹配分析

目的:分析2型糖尿病(T2DM)病人内皮型一氧化氮合酶3(NOS3)基因多态性与冠心病发病风险的分析。方法:纳入2019年12月—2021年12月于我院就诊的302例T2DM病人为研究对象,根据是否合并冠心病分为单纯T2DM组(224例)和合并冠心病组(78例)。收集病人临床资料、实验室指标、影像学资料,采用聚合酶链式反应(PCR)技术检测NOS3 G894T、NOS 3T786C多态性,对年龄、性别、吸烟史、体质指数、冠心病家族史、基础疾病、降糖方案进行倾向性评分匹配后采用Logistic回归分析T2DM病人NOS3基因多态性与冠心病发病风险的关系。结果:两组经倾向性评分匹配后有56例配对成功,匹配后一般资料比较差异无统计学意义(P>0.05);两组载脂蛋白AⅠ(ApoAⅠ)、同型半胱氨酸(Hcy)、左室射血分数(LVEF)、NOS3 G894T、NOS3 T786C多态性比较,差异有统计学意义(P<0.05)。Logistic回归分析显示,ApoAⅠ(OR=620.821)、Hcy(OR=1.823)、NOS3 G894T中TT型(OR=5.157)、NOS3 T786...     

出血性脑卒中与APM-1基因45 T/G和276 G/T多态性的关系

目的 探讨脂联素基因多态性与中国海南地区的出血性脑卒中的关系.方法 利用PCR-RFLP与测序检测APM-1中45T/G与276G/T的基因型及等位基因在120例出血性脑卒中患者及120例正常健康人中的分布特征.结果 SNP276位点的3种基因型的分布情况为脑出血组是G/G为60例;G/T 41例;T/T 19例,对照组中G/G为72例;G/T为40例;T/T为8例.而等位基因的分布在脑出血组为G等位基因是161例;T等位基因为79例,对照组G等位基因为184例;T等位基因为56例.两组的基因多态性位点上的T/T基因型与等位基因T出现的频率分布有显著性差异,有统计学意义,P＜0.05.而SNP45位点T/G基因型则无统计学差异.结论 APM-1基因的SNP276 G/T位点的TT基因型及等位基因T的变异可能是脑出血的易感因素.     

凝血酶活化纤维蛋白溶解抑制物基因编码区C1040T及G753A的多态性与脑梗死的相关性

目的探讨中国汉族脑梗死患者凝血酶活化纤维蛋白溶解抑制物(TAFI)基因编码区C1040T及G753A单核苷酸多态性与脑梗死的相关性。方法回顾性分析采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测130例脑梗死患者和118名同期行正常体检者(对照组)的TAFI基因编码区C1040T及G753A的多态性。结果脑梗死组TAFI基因G753A多态性的GG型频率41.5%(54例),A等位基因携带者频率58.5%(76例);而对照组分别为GG型频率44.9%(53例),A等位基因携带者频率55.1%(65例)。TAFI基因G753A多态性的GG型及A等位基因携带者两组频率差异无统计学意义(χ2=0.288,P=0.592)。在脑梗死组,C1040T多态性的CC型占50.0%(65例),T等位基因携带者占50.0%(65例);而对照组分别为CC型51.7%(61例),T等位基因携带者占48.3%(57例)。C1040T多态性的CC型及T等位基因携带者两组差异无统计学意义(χ2=0.071,P=0.790)。多因素Logistic回归分析显示,TAFI基因编码区G753A单核苷酸多态性(GA或AA基因型)及C1040T单核苷酸多态性(CT或TT基因型)不是脑梗死发病的独立危险因素。结论 TAFI基因编码区C1040T及G753A的多态性与脑梗死之间无显著相关性,不是脑梗死发病的独立危险因素。     

新疆哈萨克族高血压患者内皮型一氧化氮合酶基因G894T多态性研究

目的探讨哈萨克族人群内皮型一氧化氮合酶(eNOS)基因多态性与原发性高血压关联性.方法应用聚合酶链反应、限制性内切酶方法检测了新疆巴里坤县203例哈萨克族高血压病患者和190例正常人群eNOS基因G894T多态性.结果哈萨克族正常人群及高血压患者的eNOS基因G894T多态GG、GT、TT基因型频率分布分别为0.74,0.24,0.02和0.81,0.18,0.01,G和T等位基因分布频率分别为0.86,0.14和0.90,0.10,符合Hardy-Weinberg平衡.群体相关分析结果表明eNOS基因的G及T等位基因分布在高血压病组(EH)及正常血压组(NT)差异无显著性(χ2=3.580,P=0.058);基因型频率之间差异无显著性(χ2=4.037,P=0.133).然而男性EH组G等位基因频率(0.90)高于NT组(0.86);T等位基因频率(0.06)低于NT组(0.14).结论 eNOS基因G894T多态性可能与新疆巴里坤哈萨克族男性高血压有关.     

Heterozygotes of NOS3 polymorphisms contribute to reduced nitrogen oxides in high-altitude pulmonary edema

STUDY OBJECTIVES: High-altitude pulmonary edema (HAPE), which develops on exertion under hypoxic conditions, aggravates due to endothelial dysfunction. Repeat events of the disorder suggests of genetic susceptibility. Endothelial nitric oxide synthase gene (NOS3), a regulator of vasodilation, has emerged as a strong candidate marker. In the present study, we investigated G894T, 27-base-pair 4b/4a (variable number of tandem repeat), -922A/G, and -786T/C polymorphisms of NOS3, individually or in combination, for an association with HAPE. DESIGN: A cross-sectional case control study. SETTINGS: Blood samples of HAPE-resistant lowlanders (HAPE-r) were obtained at sea level, and blood samples of patients with HAPE (HAPE-p) were obtained at Sonam Norboo Memorial Hospital, Leh, at 3,500 m. PARTICIPANTS: The study groups consisted of 60 HAPE-r inducted two to three times to altitudes > 3,600 m; and 72 HAPE-p, who had HAPE on their first visit to high altitude. RESULTS: Nitrogen oxides (NOx) at 77.9 +/- 28.6 micromol/L were significantly elevated in HAPE-r as compared to 42.39 +/- 12.93 micromol/L in HAPE-p (p < 0.0001). Genotype distribution of G894T and 4b/4a polymorphisms was significantly different in the two groups (p = 0.001 and 0.009, respectively). Haplotype analysis revealed -922A/G and -786T/C polymorphisms in complete linkage disequilibrium. The wild-type haplotypes G-b (G894T, 4b/4a), G-A (G894T, -922A/G), and G-b-A (G894T, 4b/4a, -922A/G) were significantly overrepresented in HAPE-r (p < 0.0001, p = 0.03, and p = 0.02, respectively). The heterozygote genotype combination GTba as compared to wild-type combination GGbb was significantly higher in HAPE-p (chi2 = 18.62, p = 0.00009; odds ratio, 7.20; 95% confidence interval, 2.82 to 18.38). The combination of four heterozygotes GTbaAGTC was overrepresented in HAPE-p (p = 0.04), whereas the wild-type genotype combination GGbbAATT was overrepresented in HAPE-r (p = 0.002). Furthermore, the GGbb combination correlated with significantly elevated NOx as compared to remaining combinations as a whole in both HAPE-r and HAPE-p (p = 0.01 and 0.004, respectively). CONCLUSIONS: Reduced NOx and combination of heterozygotes associate with the susceptibility to HAPE. The study impels another step toward application of NOx as a diagnostic marker for HAPE. The NOS3 GTba and GTbaAGTC genotype combinations may find application as genetic markers for predicting the risk for HAPE.     

Endothelial nitric oxide synthase gene single nucleotide polymorphisms and the risk of hypertension: A meta-analysis involving 63,258 subjects

The endothelial nitric oxide synthase (eNOS) gene plays an important role in regulating vascular tone and blood pressure. Recently, the eNOS G894T and T-786C single nucleotide polymorphisms (SNPs) were intensively studied with regard to their associations with hypertension. However, the results of these studies were inconsistent. Therefore, we conducted the so far largest meta-analysis to better assess the correlations between eNOS SNPs and hypertension. Eligible articles were searched in PubMed, Medline, Embase, Scopus, and CNKI up to April 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between eNOS SNPs and the risk of hypertension. A total of 95 case–control studies involving 29,308 hypertension cases and 33,950 healthy controls were analyzed. The overall meta-analysis results showed that eNOS G894T and T-786C SNPs were both significantly associated with the risk of hypertension, the T allele of G894T SNP (G versus T, P < 0.00001, OR = 0.82, 95% CI 0.76–0.89) and C allele of T-786C SNP (T versus C, P = 0.004, OR = 0.92, 95% CI 0.87–0.97) conferred an increased susceptibility to hypertension. Further subgroup analyses yielded similar positive results for G894T SNP in essential hypertension, gestational hypertension, and Asian ethnicity, and that for T-786C SNP in essential hypertension and Asian population. Overall, our findings suggest that eNOS G894T and T-786C SNPs were both significantly correlated with hypertension. Additionally, the T allele of G894T SNP and C allele of T-786C SNP may serve as potential biological markers for hypertension susceptibility in Asians.     

The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients.

OBJECTIVES: This study sought to investigate the impact of a common T(-786)C single-nucleotide polymorphism (SNP) in the promoter of the endothelial nitric oxide synthase (eNOS, NOS3) gene on cardiovascular (CV) death in a prospective cohort study. BACKGROUND: The T(-786)C SNP eNOS gene implies a blunted endothelium-dependent vasodilation in hypertensive patients and was associated with multivessel coronary artery disease in cross-sectional studies, but it remained unsettled whether it carried prognostic information. METHODS: In consecutive white patients of the GENICA (Genetic and Environmental Factors in Coronary Atherosclerosis) study, who underwent coronary angiography between 1999 and 2001, we determined the incidence of CV death at follow-up. The eNOS T(-786)C and the exon 7 G(894)T SNPs were determined by melting curve analysis of amplicons from allele-specific fluorescence resonance energy transfer probes. Plasma levels of nitrate/nitrite, nitrotyrosine, and myeloperoxidase were also measured. The Kaplan-Meier and Cox regression analyses were used to assess the impact of SNPs on event-free survival. RESULTS: Complete follow-up data were obtained in 1,086 (98%) patients. After a median follow-up of 1,296 days (range 4 to 2,057 days), we observed 85 (8.2%) CV deaths. There was a significant impact of the T(-786)C eNOS genotype on CV death-free (p = 0.0102) survival, but no differences in CV death rates across G(894)T genotypes. The TT individuals, who showed a lower survival, exhibited higher plasma myeloperoxidase (p < 0.0001) and lower levels of nitrotyrosine (p < 0.0001) than CC patients. CONCLUSIONS: The T(-786)C SNP in the promoter of eNOS bears independent prognostic information and is associated with changes in markers of oxidant stress in high-risk white patients referred for coronary angiography.     

Influence of eNOS gene polymorphisms (894G/T; - 786C/T) on postoperative hemodynamics after cardiac surgery

BACKGROUND: Differences in vascular reactivity have been associated with variable NO release due to 894G/T and -786C/T polymorphisms of the eNOS gene. Carriers of the 894T and -786C alleles are known to have enhanced vascular responsiveness to vasoconstrictor stimulation due to decreased NO generation. Thus, we hypothesized that eNOS gene polymorphism could influence perioperative hemodynamics and catecholamine support in patients undergoing cardiac surgery with CPB. METHODS: In 105 patients undergoing elective CABG with CPB, systemic hemodynamics, cardiac index (CI), systemic and pulmonary vascular resistance indices (SVRI, PVRI) and catecholamine support were measured at baseline and 1 h, 4 h, 10 h and 24 h after CPB. Genotyping for the 894G/T and -786C/T eNOS gene polymorphisms was performed by polymerase chain reaction amplification. Patients were divided according to their genotype (894G/T: GG=group 1, GT and TT=group 2; -786C/T: TT=group 3, CT and CC=group 4). RESULTS: Genotype distribution for 894G/T polymorphism was 41% (GG), 52.4% (GT), 6.6% (TT) and for -786C/T polymorphism 37.1% (TT), 41.9% (CT) and 21% (CC). Pre- and intraoperative characteristics and systemic hemodynamics did not differ between groups. CI, SVRI and PVRI remained unaffected by genotype distribution. Statistical analysis of postoperative data revealed no difference between groups, especially for pharmacologic inotropic or vasopressor support. Also, coexistence of the 894T and -786C alleles had no impact on perioperative variables compared to homozygous 894G and -786T allele carriers. CONCLUSIONS: In contrast to current suggestions, the 894G/T and -786C/T genetic polymorphisms of the eNOS gene do not influence early perioperative hemodynamics after cardiac surgery with CPB.     

Variants of endothelial nitric oxide synthase gene are associated with components of metabolic syndrome in an Arab population

Genetics plays a crucial role in the development of metabolic syndrome (MetS). Here we examined the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and MetS in a Saudi Arabian cohort to extend the understanding of the genetic basis of MetS in diverse ethnic populations. Anthropometric, clinical and biochemical parameters as well as genotyping for 894G>T, -786T>C variants of eNOS gene by PCR-RFLP and 4a/b by direct PCR were performed in 886 Saudi Arabians (477 MetS and 409 Non-MetS). The genotype distribution (TT, p=0.001; TC, p=0.001; TC+CC, p=0.001) and allele (T, p=0.007; C, p=0.007) frequency of the -786T>C SNP were significantly different between Non-MetS and MetS subjects which remained significant after Bonferroni correction. Moreover: 1) the GT and GT+TT genotypes of the 894G>T SNP were associated with elevated blood pressure (p=0.017, and p=0.022, respectively); 2) the ab variant of 4a/b polymorphism was associated with decreased HDL levels (p= 0.044); and 3) the TC+CC genotype and C allele of the -786T>C SNP were associated with increased fasting glucose levels (p=0.039, and p=0.028, respectively). Also, G-a-C was identified as the risk haplotype for MetS susceptibility (p=0.034). The results suggest a significant association of 894G>T, 4a/b and -786T>C polymorphisms with MetS and its components is present in an Arab population. A genetic predisposition to develop abnormal metabolic phenotypes, consistent with an increased prevalence of metabolic phenotypes can be detected in this ethnic group.     

Gender-specific influence of NO synthase gene on blood pressure since childhood: the Bogalusa Heart Study

Impaired endothelial function caused by decreased NO production plays a pathophysiologic role in essential hypertension. Although cross-sectional data are available on the association between endothelial NO synthase gene polymorphisms and hypertension, whether the gene variants and their haplotypes affect the long-term cumulative burden and trend of blood pressure since childhood is not known. This aspect was examined using 4 polymorphisms and a community-based longitudinal cohort of 347 blacks and 801 whites aged 18 to 45 years who have been examined serially 4 to 13 times (7705 observations) over an on average of 23.4 years. The area under the curve calculated using a growth curve of serial measurements of mean arterial pressure was used as a long-term cumulative burden. Blacks compared with whites displayed significantly lower frequencies of the rare alleles for G894T (0.112 versus 0.325), G10T (0.209 versus 0.323), T-786C (0.147 versus 0.372), and A-922G (0.131 versus 0.355). In addition, T-786C and A-922G polymorphisms were in complete linkage disequilibrium in both races. After adjusting for age and body mass index, the 894T and 10T alleles were significantly associated with lower long-term burden of blood pressure since childhood in black females and white females, respectively. With respect to haplotypes, the G894-10T carriers compared with (G894-G10)/(G894-G10) showed significantly lower long-term burden and trend of blood pressure in white females. In conclusion, the endothelial NO synthase gene influences the long-term burden and trend of blood pressure since childhood in females and may contribute to their predisposition to hypertension.     

Association of (-)786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

AIMS/HYPOTHESIS: Endothelial derived nitric oxide synthase ( eNOS) gene polymorphisms affect eNOS activity and are associated with abnormal vasomotility and impaired local blood flow. A decrease in local blood flow has been reported to cause insulin resistance. The aim of this study was to examine a possible association of two eNOS polymorphisms, Glu298Asp (G894T) in exon 7 and (-)786T-C mutation with insulin resistance. METHODS: Genotypes of both Glu298Asp and (-)786T-C mutation were examined by the PCR-RFLP method. Plasma nitrate and nitrite concentrations were also measured. RESULTS: The allele frequencies of both polymorphisms showed no considerable differences in 233 non-diabetic subjects and 301 patients with Type II (non-insulin-dependent) diabetes mellitus. Non-diabetic subjects with the (-)786C allele had (p<0.05) higher fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the (-)786T/ (-)786T genotype. Diabetic subjects with (-)786C allele showed higher HbA(1c) than those with the (-)786T/(-)786T genotype. A euglycaemic hyperinsulinemic clamp study done on 71 of the 301 patients showed a lower glucose infusion rate in diabetic patients with the (-)786C allele than those without it. In diabetic patients with the (-)786C allele, plasma nitrate and nitrite concentrations were lower than in subjects without it (p=0.026). No differences were observed between mutant carriers of Glu298Asp and non-carriers among both non-diabetic subjects and Type II diabetic patients. CONCLUSIONS/INTERPRETATION: The (-)786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-diabetic subjects and Type II diabetic patients.     

NOS3基因多态性与高血压继发左心室肥厚的关联

目的本研究拟在中国人群中验证内皮型一氧化氮合酶基因（NOS3）多态性与高血压继发左心室肥厚的关联。方法采取病例对照研究,选择两个独立的高血压继发左室肥厚的病例和对照人群（2179和343人）,采用PCR-RFLP法研究NOS3的三个功能性多态性位点（-T786C/rs2070744、eNOS4a/b和＋G894T/rs1799983）的多态性与原发性高血压继发左室肥厚遗传易感因素的关系。所有入选者均进行心脏超声的检测。结果 NOS3的三个功能性多态性位点的基因型频率均符合Hardy-Weinberg平衡。只有＋G894T（Glu298Asp）位点与高血压继发左室肥厚的易感相关（第一个人群：OR=1.67,95%CI：1.19-2.36,P〈0.05;第二个人群：OR=1.41,95%CI：1.01-2.28,P〈0.05）,并呈隐性遗传模式。在两个独立样本中,与携带G等位基因（GT＋GG）的相比,携带TT基因型的患者的室间隔厚度、左室后壁厚度、左室重量指数和相对室壁厚度均增加（分别增加16.2%和11.7%、8.3%和7.1%、14.0%和25.1%、13.1%和16.2%）且均有统计学意义（P〈0.01）。结论 NOS3的＋G894T多态性位点可能是高血压继发左室肥厚遗传易感性的标志之一。