NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function

Aims The NADH/NADPH oxidase system plays a central role in vascular superox ide anion production, which appears to cause coronary endothelial dysfuncti on. Recently, it has been suggested that the C242T polymorphism of the NADH /NADPH oxidase p22 phox gene can reduce susceptibility to coronary artery d isease. We therefore tested whether this polymorphism is associated with an altered endothelium-dependent vasodilator capacity of human coronary arter ies in vivo. Methods and Results The vasodilator function of epicardial arteries in 93 p atients was assessed by endothelium-mediated, flow-dependent dilation and n itroglycerin, which is endothelium-independent. NADH/NADPH oxidase p22 phox polymorphism was determined by restriction fragment length polymorphism. C arriers of the CC genotype of the C242T p22 phox polymorphism (n=44) reveal ed a significantly blunted endothelium-dependent dilator response (11+/-9.2 % luminal area change vs 17+/-10%; P=0.007), which was, by multivariate ana lysis, independent of other risk factors or atherosclerosis itself. There w as only a trend towards decreased endothelium-independent dilation in patie nts bearing the p22 phox CC genotype (P=0.07). Conclusions The C242T polymorphism of the p22 phox gene is an important ind ependent determinant of coronary endothelial vasodilator function. These re sults provide the first clinical evidence for the functional significance o f a polymorphism of a gene related to superoxide anion production in the va scular wall. (Eur Heart J 2001; 22: 96-101, doi:10.1053/euhj.2000.2123) (C) 2001 The European Society of Cardiology.