Endothelial nitric oxide synthase gene is positively associated with essential hypertension
Endothelial nitric oxide synthase gene is positively associated with essential hypertension
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DOI：
10.1161/01.hyp.32.1.3
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发表时间：
1998-07-01
期刊：
影响因子：
8.3
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Miyamoto, Y;Saito, Y;Nakao, K
原发性高血压有遗传基础。越来越多的证据，包括缺乏内皮型一氧化氮合酶（eNOS）基因的小鼠动脉血压升高的发现，强烈表明NO代谢的改变与高血压有关。然而，没有报道表明eNOS基因多态性与原发性高血压相关。我们已经确定了一个错义变异，Glu 298 Asp，在eNOS基因的外显子7，并证明它与冠状动脉痉挛性心绞痛和心肌梗死。为了探讨eNOS基因在原发性高血压中的遗传参与，我们研究了原发性高血压与几种多态性之间的可能关联，包括Glu 298 Asp变体、内含子4中的可变数目串联重复序列（eNOS 4 b/4a）以及内含子18和23中的两种多态性。我们使用来自日本京都（n=458; 240名血压正常者对218名高血压受试者）和熊本（n=421; 223名血压正常者对187名高血压受试者）的两个独立人群进行了一项大规模的遗传相关性研究。在两组中，一种新的编码变体Glu 298 Asp显示与原发性高血压有很强的相关性（京都：比值比，2.3 [95%置信区间，1.4 - 3.9];熊本：比值比，2.4 [95%置信区间，1.4 - 4.0]）。高血压组298 Asp等位基因频率显著高于正常血压组（京都：0.103比0.050，P
Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyoto: odds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamoto: odds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto: 0.103 versus 0.050, P