High CA repeat numbers in intron 13 of the endothelial nitric oxide synthase gene and increased risk of coronary artery disease

Endothelial nitric oxide synthase (eNOS) plays a key role in vascular homeo stasis. Because its product, nitric oxide, possesses vasodilatory and antia therogenic properties, an altered eNOS function might promote atheroscleros is, We investigated the association between variations in CA repeat copy nu mber [(CA), polymorphism] in intron 13 of the eNOS gene and the risk of cor onary artery disease, (CA), polymorphism was investigated in 1000 consecuti ve patients with angiographically confirmed coronary artery disease and 100 0 age- and gender-matched control subjects by a PCR-based fragment length c alculation, Twenty-eight different alleles were identified containing 17-44 CA repeats. The presence of one allele containing greater than or equal to 38 repeats was associated with an excess risk of coronary artery disease ( odds ratio 1.94, 95% confidence interval 1.31-2.86, P = 0.001). Carriers of alleles containing greater than or equal to 38 CA repeats were, in particu lar, overrepresented in the subgroup without common cardiovascular risk fac tors (odds ratio 3.39, 95% confidence interval 1.30-8.86, P = 0.009). Logis tic regression analysis revealed that the (CA), polymorphism proved to be a n independent risk factor (relative risk 2.17, 95% confidence interval 1.44 -3.27, P = 0.0002). Our findings indicate that high numbers of CA repeats i n intron 13 of the eNOS gene are associated with an excess risk of coronary artery disease, Pharmacogenetics 10:133-140 (C) 2000 Lippincott Williams & Wilkins.