A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis

Background and Purpose-Endothelium-derived NO is formed from L-arginine by endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. B ecause several studies have indicated that NO plays a key role in the devel opment of the atherosclerotic process, we investigated whether common varia nts in the eNOS gene are associated with an increased risk of plaque on car otid arteries. Methods-We studied 375 subjects attending the hypertension center of our in stitution to be screened for arterial hypertension. The examined subjects w ere classified according to the presence of carotid plaques (intima-media t hickness greater than or equal to1.5 mm), and 2 intronic (CA and 27-bp repe ats) polymorphisms and 1 exonic (Glu298Asp) polymorphism of the eNOS gene w ere explored. Results-Only the Glu298Asp polymorphism of eNOS was associated with the pre sence of carotid plaques (P<0.05). In particular, there was an excess of ho mozygotes for the Asp298 variant among subjects with carotid plaques, where as the number of subjects who had the Glu298 allele in exon 7 of the eNOS g ene was equally distributed in both study groups. Interestingly, the risk o f having carotid plaques was increased <approximate to>3 times in subjects who were homozygotic for the Asp298 variant compared with subjects who were homozygotic for the Glu298 variant and was independent of the other common risk factors (age, blood pressure, and smoking). Conclusions-Homozygosity for Asp298, a common variant of the eNOS gene, is an independent risk factor for carotid atherosclerosis in this study popula tion.