Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease

Background: Plasma NOx (nitrate and nitrite) is a stable end product of the vasodilator NO. Several polymorphisms in the endothelial constitutive NO s ynthase (ecNOS) gene have been reported, including the 4a/4b VNTR polymorph ism in intron 4, the E298D mutation in exon 7, and the G10-T polymorphism i n intron 23. The aims of this study were to examine plasma NOx in patients with coronary artery disease (CAD) and to assess the association between pl asma NOx concentrations and the three ecNOS gene polymorphisms. Methods: Plasma NOx was measured in samples from 128 healthy controls and f rom 110 CAD patients at least 2 months after myocardial infarction. Three g enetic polymorphisms that are known or have been suggested to be associated with plasma NOx concentration were also analyzed by PCR-restriction fragme nt length polymorphism. Results: Median plasma NOx was significantly higher (P <0.001) in CAD patie nts (95.9 mu mol/L) than in controls (73.8 mu mol/L). Furthermore, the medi an plasma NOx was significantly higher (P <0.001) in hypertensive CAD patie nts (116.0 mu mol/L) than in controls and normotensive CAD patients (86.0 m u mol/L). The G-allele frequency of the G10-T polymorphism in intron 23 was significantly higher:in CAD patients than in controls. Other polymorphisms showed no differences in allelic frequencies among the control and CAD gro ups. In: controls, individuals with the E298D mutation in exon 7 (136.1 mu mol/L) showed significantly higher (P = 0.001) median plasma NOx than those without this mutation (64.5 mu mol/L). Conclusions: Plasma NOx was higher in hypertensive CAD patients than in nor motensive CAD patients and controls. The E298D polymorphism of the ecNOS ge ne was associated with increased plasma NOx. Further study is needed to und erstand the gene expression and enzyme activity of ecNOS and their associat ion with genotypes. (C) 2000 American Association for Clinical Chemistry.