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European Heart Journal 2001 22(1):96-101; doi:10.1053/euhj.2000.2123
Copyright © 2001 by the European Society of Cardiology.
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NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function

V. Schächingerf1, M.B. Britten, S. Dimmeler and A.M. Zeiher

Department of Internal Medicine, Division of Cardiology, J. W. Goethe-University, Frankfurt, Germany

revised January 10, 2000; accepted January 14, 2000

Abstract

Aims The NADH/NADPH oxidase system plays a central role in vascular superoxide anion production, which appears to cause coronary endothelial dysfunction. Recently, it has been suggested that the C242T polymorphism of the NADH/NADPH oxidase p22 phox gene can reduce susceptibility to coronary artery disease. We therefore tested whether this polymorphism is associated with an altered endothelium-dependent vasodilator capacity of human coronary arteries in vivo.

Methods and Results The vasodilator function of epicardial arteries in 93 patients was assessed by endothelium-mediated, flow-dependent dilation and nitroglycerin, which is endothelium-independent. NADH/NADPH oxidase p22 phox polymorphism was determined by restriction fragment length polymorphism. Carriers of the CC genotype of the C242T p22 phox polymorphism (n=44) revealed a significantly blunted endothelium-dependent dilator response (11±9·2% luminal area change vs 17±10%;P=0·007), which was, by multivariate analysis, independent of other risk factors or atherosclerosis itself. There was only a trend towards decreased endothelium-independent dilation in patients bearing the p22 phox CC genotype (P=0·07).

Conclusions The C242T polymorphism of the p22 phox gene is an important independent determinant of coronary endothelial vasodilator function. These results provide the first clinical evidence for the functional significance of a polymorphism of a gene related to superoxide anion production in the vascular wall.

Key Words: Risk factors, endothelial dysfunction, genes, free radicals, coronary artery disease

f1 Correspondence: Volker Schächinger, MD, Department of Internal Medicine, Division of Cardiology, J. W. Goethe-University, Theodor-Stern-kai 7, Germany

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