Lack of evidence for association between the endothelial nitric oxide synthase gene and hypertension

Significant association between a G1u298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene and essential hypertension was recently reported in Japanese populations, with the 298Asp variant showing a higher prevalence in hypertensive patients (10.3% to 12.0%) than in normotensive s ubjects (5.0% to 5.8%). In contrast, another study demonstrated that the 29 8Glu variant was significantly associated with hypertension in a Caucasian population. We therefore undertook an extensive association study in Japane se to resolve these contradictory claims. A total of 1165 individuals were selected from clinic outpatients and hospital staff in a single institution . The relevance of the G1u298Asp polymorphism to hypertension in this popul ation was tested in 2 ways. First, a case-control study was conducted in 54 9 hypertensive and 513 normotensive subjects within the study population, w ith the chi(2) statistic used to test the significance of an association be tween eNOS genotype and the presence of hypertension. Second, an ANOVA was used to test the significance of an association between eNOS genotype and t he level of blood pressure within the entire population except for 167 hype rtensive subjects who had been under treatment for hypertension. No signifi cant association was observed in either of the statistics tested. Allele fr equencies of 298Asp were concordant across the panels: 8.4% in hypertensive subjects, 8.2% in normotensive subjects, and 7.9% and 9.5% in 2 additional sample populations used as reference panels, Taken together, our results d o not support the previous observation that the molecular variant of the eN OS gene may confer principal susceptibility for essential hypertension but rather suggest the existence of sampling variation.