Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans

Biochemical and Biophysical Research Communications
T TsukadaJ Igari

Abstract

Nitric oxide (NO) synthesized by the vascular endothelium regulates mammalian blood vessels and other systems in humans. Recently, an endothelial nitric oxide synthase (ecNOS) gene polymorphism, the 27-bp repeat in intron 4 (ecNOS4), was reported to be related to the pathogenesis of coronary heart disease and terminal renal failure. We analyzed this polymorphism in a group of 413 healthy subjects, and measured their plasma nitrite and nitrate (NOx) levels. The frequency of the b allele was 89.8% , and the frequency of the a allele was 10.2%. The frequency of ecNOS4 b/b, ecNOS4 b/a, and ecNOS4 a/a in the healthy subjects in this study was 0.814 (n=336), 0.169 (n=70) and 0.017 (n=7), respectively. Using this polymorphism as a DNA marker, we found a strong association between the alleles of the ecNOS gene polymorphism and the plasma NOx levels. The basal NO metabolite levels were 28.8 micromol/L in subjects with ecNOS4 a/a, 31.4 micromol/L in those with ecNOS4 b/a, and 35.5 micromol/L in those with ecNOS4 b/b. The mean plasma NOx level of the subjects who were homozygous for the a allele was nearly 20% lower than in the subjects with the b allele. The plasma NOx level of the subjects with the a allele was 31.2+/-2.00 micromol/L, a...Continue Reading

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