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The significance of endothelial nitric oxide synthase gene polymorphisms as genetic markers of hypertensive disorders

内皮一氧化氮合酶基因多态性作为高血压疾病遗传标记的意义

基本信息

批准号：
12672236
负责人：
YASUJIMA Minoru
金额：
$ 2.18万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672236/
关键词：
gene polymorphism hypertension restriction enzyme fragment length polymorphism (RFLP)end-stage renal disease chronic glomerulonephritis diabetic nephropathy angiotensin coverting enzyme I D polymorphism Y chromosome Alu insertion polymorp

项目摘要

The nitric oxide (NO) plays an important role in the regulation of blood pressure and regional blood flow. Decreased NO activity could contribute to renal vasoconstriction, NaCl retention, and elevated blood pressure. The endothelial NO synthase (ecNOS) gene has been raised as a candidate of genetic risk factor for the development of hypertension and renal diseases. To establish the significance of ecNOS gene polymorphisms as genetic markers of hypertension and its complications, we studied an association between ecNOS gene polymorphisms and hypertension in Japanese subjects. Patients with end-stage renal disease (ESRD) and general regional residents were also enrolled in this study. The genotypes of the ecNOS Glu298Asp and 4b/a variations were determined with PCR based methods including restriction enzyme fragment length polymorphism. In addition, the linkage disequilibrium between 2 ecNOS variations and angiotensin coverting enzyme I/D polymorphism and Y chromosome Alu insertion polymorphism (YAP) was examined. Positive association was found between hypertension and ecNOS Glu298Asp gene polymorphism. However, ecNOS 4b/a gene polymorphism was not associated with hypertension. Systolic blood pressure was significantly lower in the Glu/Glu genotype than in Glu/Asp+Asp/Asp genotypes. Whereas neither Glu298Asp nor 4b/a variations had an association with ESRD including chronic glomerulonephritis and diabetic nephropathy. A significant linkage disequilibrium was found between ecNOS 4b/a gene polymorphism and YAP.These results suggest that the ecNOS Glu298Asp gene polymorphism may be genetic-susceptibility factors for hypertension.

一氧化氮（nitric oxide，NO）在血压和局部血流的调节中起重要作用。NO活性降低可导致肾血管收缩、NaCl潴留和血压升高。内皮型一氧化氮合酶（endothelial NO synthase，ecNOS）基因已被认为是高血压和肾脏疾病的遗传危险因子。为了建立ecNOS基因多态性作为高血压及其并发症的遗传标记的意义，我们研究了日本受试者的ecNOS基因多态性与高血压之间的关联。终末期肾病（ESRD）患者和一般地区居民也入组本研究。采用PCR技术和限制性内切酶片段长度多态性分析方法检测ecNOS Glu 298 Asp和4 b/a变异的基因型。此外，还分析了2种ecNOS变异与血管紧张素转换酶I/D多态性和Y染色体Alu插入多态性（雅普）之间的连锁不平衡。高血压与ecNOS Glu 298 Asp基因多态性呈正相关。然而，ecNOS 4 b/a基因多态性与高血压无关。Glu/Glu基因型的收缩压显著低于Glu/Asp+Asp/Asp基因型。而Glu 298 Asp和4 b/a变异与ESRD包括慢性肾小球肾炎和糖尿病肾病均无相关性。ecNOS 4 b/a基因多态性与雅普存在连锁不平衡，提示ecNOS Glu 298 Asp基因多态性可能是高血压的遗传易感因素。