C242T polymorphism of NADPH oxidase p22 PHOX gene and ischemic cerebrovascular disease in the Japanese population.

BACKGROUND AND PURPOSE Superoxide has been implicated in the pathogenesis of ischemic stroke and atherosclerosis. NADPH oxidase, a major source of superoxide generation in neutrophils and the vascular system, plays a critical role in ischemic injury and atherogenesis. Recently, an association between the C242T polymorphism of p22 PHOX, an essential component of NADPH oxidase, and coronary artery disease (CAD) has been reported in several studies. To investigate the relationship between the C242T polymorphism of p22 PHOX and ischemic cerebrovascular disease (CVD), we conducted a case-control study. METHODS We recruited 226 CVD patients (atherothrombotic infarction, lacunar infarction, and transient ischemic attack) and 301 control subjects and analyzed C242T polymorphism of p22 PHOX by detection of restriction fragment length polymorphism. RESULTS The TC+TT genotype frequencies in the CVD group and control group were 21.7% and 13.3%, respectively, and the prevalence of the TC+TT genotype was significantly higher in the CVD patients (chi(2)=6.477, P=0.01, OR 1.81, 95% CI 1.15 to 2.86). Analysis by CVD subtypes showed that the OR for the TC+TT genotype was higher in the CVD patients with atherothrombotic infarction than in those with lacunar infarction and transient ischemic attack. CONCLUSIONS The C242T polymorphism of the NADPH oxidase p22 PHOX gene is a novel pathogenetic risk factor for CVD.