Endothelial nitric oxide gene haplotype reduces the effect of a single bout of exercise on the vascular reactivity in healthy subjects

Abstract

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene reduce shear stress-induced nitric oxide production. Thus, we investigated the individual and combined impact of 3 variants in the eNOS gene (-786T>C, intron 4b4a, and 894G>T) on vascular reactivity before and after exercise. Sedentary, healthy subjects were studied (105 women/26 men, age 32 ± 1 years [mean ± standard error of the mean]). Genotypes were determined by polymerase chain reaction restriction fragment length polymorphism, and haplotypes were determined by a Bayesian-based algorithm. Vascular reactivity was evaluated by the percentage of change in forearm vascular conductance provoked by 5 minutes of circulatory occlusion before (baseline) and 10, 60, and 120 minutes after a maximal cardiopulmonary exercise test. Vascular reactivity increased 10 minutes after exercise in the entire sample (baseline: 218 ± 11% vs 10 minutes: 284 ± 15%, P < 0.001), remained increased at 60 minutes (239 ± 12%, P = 0.02 vs baseline), and returned to baseline at 120 minutes (210 ± 10%, P = 0.83 vs baseline). Genotype analysis showed that subjects with the 894G>T polymorphism had lower vascular reactivity than wild counterparts (group effect, P = 0.05). Furthermore, subjects with haplotype 2 (H2), containing the -786T>C and 894G>T polymorphisms, had lower vascular reactivity than wild counterparts (haplotype 1 [H1]) (group effect, P = 0.05), whereas subjects with haplotype 4 (H4), containing only the 894G>T polymorphism, had vascular reactivity similar to that of wild counterparts (H1) (group effect, P = 0.35). Altogether, these results indicate that the 894G>T polymorphism reduced exercise-mediated increase in vascular reactivity, particularly when it occurred concomitantly with the -786T>C polymorphism.