The p22 phox A640G gene polymorphism but not the C242T gene variation is associated with coronary heart disease in younger individuals

Abstract

Background: Most recently, evidence has been presented that the NADH/NADPH oxidase p22 phox C242T, but not the A640G 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 in 2205 male Caucasians whose coronary anatomy was defined by means of coronary angiography. In the total population and in high and low risk groups the relative frequencies of the C242T alleles were essentially the same in patients without or with CAD and in individuals without or with myocardial infarction. In contrast, the G allele of the A640G polymorphism was significantly more frequent in subjects without CAD than in patients with CAD (Odds ratio (OR) 0.74 (0.57-0.98); P = 0.038 in multiple logistic regression (MLR)). Correspondingly, the AA genotype of A640G was preferentially found in patients with CAD. These associations did not disappear when the analyses were corrected for multiple comparisons for other gene polymorphisms (ACE I/D gene variation, angiotensinogen T174M and M235T gene polymorphisms, AT1 receptor gene variation, phox C242T gene polymorphism, paraoxonase PON54 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 of the A640G gene variation with the presence and extent of CAD was not only identified in the total sample, but was even stronger in various high risk subpopulations of younger individuals (e.g. with hypertension with or without increased apolipoprotein B plasma levels).

Conclusions: Our observations allow the assumption that the p22 phox A640G gene polymorphism is independently associated with the presence and extent of coronary artery disease.