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

一氧化氮（NO）在调节血压和局部血流中起着重要作用。NO活性降低可导致肾血管收缩、NaCl滞留和血压升高。内皮NO合成酶（ecNOS）基因已被认为是高血压和肾脏疾病的潜在遗传危险因素。为了确定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中ecNOS基因多态性与高血压的关系。终末期肾病（ESRD）患者和一般地区居民也被纳入本研究。采用限制性内切酶片段长度多态性等PCR方法对ecNOS Glu298Asp和4b/a变异进行基因型分析。此外，还检测了2个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（YAP）之间的连锁不平衡。高血压与ecNOS Glu298Asp基因多态性呈正相关。然而，ecNOS 4b/a基因多态性与高血压无关。Glu/Glu基因型患者的收缩压明显低于Glu/Asp+Asp/Asp基因型患者。然而，Glu298Asp和4b/a变异均与ESRD（包括慢性肾小球肾炎和糖尿病肾病）无关。ecNOS 4b/ A基因多态性与YAP之间存在显著的连锁不平衡。提示ecNOS Glu298Asp基因多态性可能是高血压的遗传易感因素。

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.