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

Stangl, Karla; Cascorbi, Ingolfb; Laule, Michaela; Klein, Thomasb; Stangl, Verenaa; Rost, Stephana; Wernecke, Klaus D.c; Felix, Stephan B.a; Bindereif, Albrechtd; Baumann, Gerta; Roots, Ivarb

Original Article
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Endothelial nitric oxide synthase (eNOS) plays a key role in vascular homeostasis. Because its product, nitric oxide, possesses vasodilatory and antiatherogenic properties, an altered eNOS function might promote atherosclerosis. We investigated the association between variations in CA repeat copy number [(CA)n polymorphism] in intron 13 of the eNOS gene and the risk of coronary artery disease. (CA)n polymorphism was investigated in 1000 consecutive patients with angiographically confirmed coronary artery disease and 1000 age- and gender-matched control subjects by a PCR-based fragment length calculation. Twenty-eight different alleles were identified containing 17–44 CA repeats. The presence of one allele containing ≥ 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 ≥ 38 CA repeats were, in particular, overrepresented in the subgroup without common cardiovascular risk factors (odds ratio 3.39, 95% confidence interval 1.30–8.86, P = 0.009). Logistic regression analysis revealed that the (CA)n polymorphism proved to be an 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 in intron 13 of the eNOS gene are associated with an excess risk of coronary artery disease.

aMedizinische Klinik mit Schwerpunkt Kardiologie, Angiologie und Pneumologie, bInstitut für Klinische Pharmakologie, cInstitut für Medizinische Biometrie and dInstitut für Biochemie, Charité, Campus Mitte, Humboldt Universität zu Berlin, Germany

Received 27 May 1999 accepted 17 September 1999

Correspondence to Karl Stangl, Medizinische Klinik mit Schwerpunkt Kardiologie, Angiologie und Pneumologie, Charité, Campus Mitte, Humboldt-Universität zu Berlin, Schumannstrasse 20/21, D-10098 Berlin, Germany Tel: +49 30 2802 5885; fax +49 30 2802 3996; e-mail: karl.stangl@charite.de

© 2000 Lippincott Williams & Wilkins, Inc.