C242T polymorphism of NADPH oxidase p22 PHOX gene and ischemic cerebrovascular disease in the Japanese population.
OBJECTIVE
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.
Ito
D
D
Departments of Neurology, School of Medicine, Keio University, Tokyo, Japan.
Murata
M
M
Watanabe
K
K
Yoshida
T
T
Saito
I
I
Tanahashi
N
N
Fukuuchi
Y
Y
D044466:Asian People / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000235:genetics; D020767:Intracranial Thrombosis / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000235:genetics; D007564:Japan; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009252:NADPH Dehydrogenase / Q000235:genetics*; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012016:Reference Values
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase