T-786C内皮型一氧化氮合酶基因型是GENICA研究中白种人患者患冠状动脉疾病的一个新的风险因素。

The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study.

作者信息

Rossi Gian Paolo, Cesari Maurizio, Zanchetta Mario, Colonna Stefania, Maiolino Giuseppe, Pedon Luigi, Cavallin Martina, Maiolino Pietro, Pessina Achille C

机构信息

Department of Clinical and Experimental Medicine, Clinica Medica 4 University Hospital, University of Padua, via Giustiniani 2, 35126 Padua, Italy.

出版信息

J Am Coll Cardiol. 2003 Mar 19;41(6):930-7. doi: 10.1016/s0735-1097(02)03012-7.

DOI:10.1016/s0735-1097(02)03012-7

PMID:12651036

Abstract

OBJECTIVES

We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD).

BACKGROUND

Endothelial dysfunction foretells cardiovascular events and can be genetically determined.

METHODS

We genotyped for the promoter (T(-786)C) and exon 7 (Glu298Asp, G(894)T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T(-786)C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD.

RESULTS

The overall genotype distribution of T(-786)C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T(-786)C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T(-786)C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041).

CONCLUSIONS

The C allele at the T(-786)C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.

摘要

目的

我们研究了内皮型一氧化氮合酶（eNOS）基因启动子区域和第7外显子的多态性与冠状动脉疾病（CAD）之间的关联。

背景

内皮功能障碍预示着心血管事件，并且可能由基因决定。

方法

我们对1225名受试者的启动子（T（-786）C）和第7外显子（Glu298Asp，G（894）T）多态性进行了基因分型；其中1106名是连续接受冠状动脉造影的患者，119名是没有任何心血管危险因素的对照受试者。基因分型采用聚合酶链反应产物的熔解曲线分析，等位基因特异性受体和供体探针分别在5'端和3'端用LCRed640和荧光素标记；通过定量冠状动脉造影评估CAD。我们对T（-786）C、错义Glu298Asp变异以及其他冠状动脉危险因素对双支和三支血管CAD的影响进行了多因素逻辑回归分析。

结果

T（-786）C（CC = 17.7%，CT = 40.4%，TT = 41.9%）和Glu298Asp（GG = 43.3%，GT = 37.0%，TT = 19.7%）的总体基因型分布符合哈迪-温伯格平衡。回归分析表明，T（-786）C而非错义Glu298Asp变异可独立于其他危险因素显著预测CAD。与TT纯合子相比，携带C等位基因的受试者患双支或三支血管CAD的比值比显著增加（p = 0.002），为1.672（95%置信区间，1.062至2.527）。亚组分析证实了T（-786）C多态性在男性（p = 0.007）、吸烟者（p = 0.001）、60岁以上受试者（p = 0.007）、高胆固醇血症患者（p = 0.011）、低高密度脂蛋白胆固醇患者（p = 0.006）以及超重或肥胖患者（p = 0.041）中的这种作用。