The p22 phox A(640)G gene polymorphism but not the C242T gene variation isassociated with coronary heart disease in younger individuals

Background. Most recently, evidence has been presented that the NADH/NADPH oxidase p22 phox C242T, but not the A(640)G gene polymorphism is associated with a reduced risk of coronary artery disease (CAD), Methods and results. We analysed the relationships of both p22 phox gene polymorphisms to CAD i n 2205 male Caucasians whose coronary anatomy was defined by means of coron ary angiography. In the total population and in high and low risk groups th e relative frequencies of the C242T alleles were essentially the same in pa tients without or with CAD and in individuals without or with myocardial in farction. In contrast, the G allele of the A(640)G polymorphism was signifi cantly more frequent in subjects without CAD than in patients with CAD (Odd s ratio (OR) 0.74 (0.57 - 0.98); P = 0.038 in multiple logistic regression (MLR)). Correspondingly, the AA genotype of A(640)G was preferentially foun d in patients with CAD. These associations did not disappear when the analy ses were corrected for multiple comparisons for other gene polymorphisms (A CE I/D gene variation, angiotensinogen T174M and M235T gene polymorphisms, AT(1) receptor gene variation, phox C242T gene polymorphism, paraoxonase PO N54 and PON191 gene variations) (2p = 0.01 in MLR for the presence of CAD: 2p = 0.039 in multiple regression for the extent of CAD). The association o f the A(640)G gene variation with the presence and extent of CAD was not on ly identified in the total sample, but was even stronger in various high ri sk subpopulations of younger individuals (e.g. with hypertension with or wi thout increased apolipoprotein B plasma levels). Conclusions. Our observati ons allow the assumption that the p22 phox A(640)G gene polymorphism is ind ependently associated with the presence and extent of coronary artery disea se. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.