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

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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.