Endothelial nitric oxide synthase Glu²⁹⁸→Asp polymorphism, carotid atherosclerosis and intima-media thickness in a general population sample

The Glu²⁹⁸→Asp (E298D; 894G→T) polymorphism of eNOS (endothelial nitric oxide synthase) has been related with cardiovascular disease. In the present study, we investigated the association of Glu²⁹⁸→Asp with atherosclerotic plaques in different carotid vessel segments and with carotid IMT (intima-media thickness). The Glu²⁹⁸→Asp eNOS polymorphism was determined by 5′-exonuclease assay among 2448 participants of the SHIP (Study of Health in Pomerania). Mean and maximum common carotid IMT, as well as carotid atherosclerosis, were measured by high-resolution ultrasound. The Asp/Asp²⁹⁸ genotype was associated with an increased risk of atherosclerotic plaques at the level of the common carotid arteries [multivariate odds ratio, 1.57 and 95% CI (confidence interval), 1.05–2.34; P=0.025], but not in the carotid bifurcations or internal or external carotid arteries. Glu²⁹⁸→Asp genotype was not associated with carotid IMT in the whole sample. However, the Asp/Asp²⁹⁸ genotype was independently associated with both higher mean [adjusted increase by 0.046 mm (95% CI, 0.013–0.078); P=0.006] and maximum carotid IMT [0.137 mm (95% CI, 0.064–0.209); P<0.001] in the low-risk group of subjects without carotid atherosclerosis. In conclusion, the Asp/Asp²⁹⁸ genotype is associated with atherosclerosis in the common carotid arteries and, in a low-risk group, also with carotid IMT. This suggests that the association of the Glu²⁹⁸→Asp genotype with atherosclerosis in the carotid arteries is site-specific and is modified by overall cardiovascular risk.