The Glu-298 -> Asp (894G -> T) mutation at exon 7 of the endothelial nitric oxide synthase gene and coronary artery disease

We examined associations between the endothelial nitric oxide synthase (eNO S) gene Glu-298-->Asp (894G-->T) mutation and the occurrence and severity o f angiographically defined coronary artery disease (CAD). eNOS mediates bas al vascular wall nitric oxide production, and altered nitric oxide producti on has been implicated in atherosclerosis. The newly identified eNOS Glu-29 8-->Asp mutation in exon 7 is common and likely to be functional. It was fo und to be associated with myocardial infarction (MI) in Japanese but not in whites. We genotyped 763 white Australians undergoing coronary angiography for the eNOS Glu-298-->Asp mutation. The frequencies of the eNOS GG, TG an d TT genotypes were 47.8%, 41.2% and 11.0% in men and 45.2%, 41.1% and 13.7 % in women with CAD, and were not significantly different from those withou t CAD (43.2%, 40.7% and 16.0%, P=0.423 in men; 40.2%. 48.1% and 11.7%, P=0. 582 in women). The mutation was also not associated with MI (P=0.469 in mal es; P=0.389 in females) or with the number of significantly stenosed vessel s (P=0.954; P=0.734). The "T" allele frequency (32.5%) was much greater tha n that reported for the Japanese population (7.8% in controls and 10.0% in MI patients). In conclusion, the eNOS Glu-298-->Asp mutation is common, occ urring with an allele frequency of 32.5%, but is not associated with either the occurrence or severity of CAD in the Australian population or with oth er established coronary risk factors assessed in our study. The mutation is significantly more frequent in the Australian than in the Japanese.