Variant of endothelial nitric oxide synthase gene determines severity of atherosclerosis

A common variant of an enzyme which produces nitric oxide in endothelial cells may in future become a genetic marker for susceptibility to atherosclerosis.

Researchers in Italy have shown for the first time that the polymorphic Glu→Asp variant of endothelial nitric oxide synthase (eNOS) is linked to the extent and severity of coronary artery disease (CAD).

Of the three possible eNOS genotypes, the Asp/Asp homozygous genotype had a higher frequency in patients with CAD than controls (15.9% v 6.1%) whereas the Glu/Glu and Glu/Asp genotypes did not. The likelihood of having the Asp/Asp genotype and CAD was 2.9 (95% confidence interval 1.2 to 6.8) when compared with the other genotypes combined. Multiple regression showed that Asp/Asp was an independent risk factor for CAD. This genotype had no relation with other known risk factors but was significantly associated with number of narrowed vessels (mean (SEM) 2.3 (0.1) for Asp/Asp v 1.9 (0.1) for Glu/Glu, and 1.8 (0.1) for Glu/Asp, respectively) and higher Duke score, denoting severity of CAD (mean (SEM) 56.1(3.1), 46.7(2.0), and 46.1(1.9), respectively).

The study population included 201 patients with CAD, who had more than 50% narrowing of more than one vessel on angiography, and 114 controls with no CAD awaiting valve replacements. Amplification of DNA by polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis were used to ascertain eNOS genotype.

Nitric oxide in endothelium inhibits many pathogenetic mechanisms in atherosclerosis, and the Glu²⁹⁸→Asp polymorphism has previously been reported in CAD and myocardial infarction.