Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension
Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension
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DOI：
10.1016/s0895-7061(00)00282-x
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发表时间：
2000-09-01
影响因子：
3.2
通讯作者：
Morris, BJ
中科院分区：
文献类型：
--
作者：
Benjafield, AV;Morris, BJ
由 NOS3 编码的内皮一氧化氮合酶 (eNOS) 是血管舒缩张力和外周阻力的有效调节剂。同类实验表明，含有大鼠 eNOS 基因的染色体片段导致大鼠自发性高血压 (HT)。然而，NOS3 在原发性高血压 (HT) 发病中的作用尚存在争议。因此，我们决定在一组具有显着能力显示现有遗传关联的患者中测试 NOS3 多态性。 112 名 HT 受试者有两名 HT 父母，血压正常 (NT) 受试者有两名 NT 父母。所有人都是盎格鲁凯尔特白人。两个最有希望的多态性，即内含子 4 中的双等位可变串联重复数 (VNTR) 和导致氨基酸变化的外显子 7 变体 (Glu298Asp)，通过 PCR 进行了基因分型（如果是后者，则进行 BanII 消化）。 NTR 次要等位基因的频率在 NT 受试者中为 0.11，在 HT 受试者中为 0.10 (P = .9)。对于外显子 7 变体，每个组中的 Asp298 频率分别为 0.30 和 0.32 (P = .6)。跟踪结果显示，Asp298 等位基因随体重指数升高 (P = .034)，而 VNTR 次要等位基因则随 LDL 升高 (P = .007) 和 HDL 降低 (P = .048)。总之，我们在研究人群中发现 NOS3 标记物与 HT 没有关联。然而，基因型对血脂和体重指数可能产生的影响可能值得进一步研究，特别是考虑到可能与心脏病相关。 Am J Hypertens 2000；13:994-998 (C) 2000 美国高血压杂志有限公司。
Endothelial nitric oxide synthase (eNOS), encoded by NOS3, is a potent regulator of vasomotor tone and peripheral resistance. Congenic experiments indicate that a chromosomal segment containing the rat eNOS gene contributes to rat spontaneous hypertension (HT). A role for NOS3 in onset of essential hypertension (HT) is, however, controversial. We therefore decided to test NOS3 polymorphisms in a set of patients who have an accentuated ability to show an existing genetic association. The 112 HT subjects had two HT parents and the normotensive (NT) subjects had two NT parents. All were Anglo-Celtic whites. The two most promising polymorphisms, viz, a biallelic variable number of tandem repeats (VNTR) in intron 4 and an exon 7 variant that leads to an amino acid change (Glu298Asp), were genotyped by PCR (and BanII digestion in the case of the latter). Frequency of the minor allele of the VNTR was 0.11 in the NT and 0.10 in the HT subjects (P = .9). For the exon 7 variant, Asp298 frequency was 0.30 and 0.32 in each respective group (P = .6). Tracking was seen for the Asp298 allele with elevation in body mass index (P = .034), and the minor allele of the VNTR with elevation in LDL (P = .007) and reduction in HDL (P = .048). In conclusion, we saw no association of NOS3 markers with HT in the population studied. However, possible genotypic effects on plasma lipids and body mass index might warrant further studies, especially in view of possible associations with heart disease. Am J Hypertens 2000;13:994-998 (C) 2000 American Journal of Hypertension, Ltd.