Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans

Abstract Background The role of eNOS gene polymorphisms on plasma nitrite or nitrate (NOx) level, endothelial function, and blood pressure (BP) remains unclear. Methods We estimated the relationship of eNOS polymorphisms (the T−786C in the 5′-flanking promoter region, T−786C; 27-bp repeat in intron 4, eNOS4; and Glu298Asp in exon 7, G894T) with plasma NOx level, brachial endothelial function assessed by ultrasound measure of brachial artery flow-mediated dilation (FMD), and BP in 60 healthy African Americans, 30 men and 30 women aged 18 to 73 years. Results Among them, 73.1%, 23.9%, and 3.0% carried TT, TC, and CC of T−786C, respectively, 14.5%, 27.5%, 53.6%, and 1.4% carried aa, ab, bb, and bc of eNOS4 polymorphism, respectively, and 70.4%, 23.9%, and 5.6% carried GG, GT, and TT of G894T, respectively. G894T and eNOS4 were observed in linkage disequilibrium. Mean values of age, plasma NOx, FMD, systolic and diastolic BPs were not significantly different (P> .05) by eNOS polymorphisms. Plasma NOx level was found to be associated with systolic BP (r = 0.51, P = .03), and diastolic BP (r = 0.41, P = .08), but not with FMD, in individuals with “a” allele of eNOS4 polymorphism after adjustment for age, body mass index, serum glucose, and smoking status. Conclusions We reveal a positive association between plasma NOx level and BP in normotensive African Americans who carry the “a” allele of eNOS4. Because the frequency of the rare allele “a” is significantly higher in African Americans than in other ethnic groups, this finding may provide a clue to understanding the genetic susceptibility to hypertension in African Americans.