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Circulation. 1998 Jan 20;97(2):135-7.

Polymorphism of the NADH/NADPH oxidase p22 phox gene in patients with coronary artery disease.

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First Department of Internal Medicine, Kobe University School of Medicine, Japan.



Oxidative stress in the vasculature has been implicated in the pathogenesis of coronary artery disease (CAD). NADH/NADPH oxidase is a key enzyme of superoxide production in the vasculature. p22 phox, an essential component of NADH/NADPH oxidase, has four types of polymorphism. The C242T polymorphism changes histidine-72 to tyrosine, located in the potential heme-binding sites, whereas A640G polymorphism is located in the 3' untranslated region.


We investigated whether these polymorphisms were associated with risk of CAD by use of restriction fragment length polymorphism (RFLP). The prevalence of the TC + TT genotype of the C242T polymorphism was significantly more frequent in control subjects (n=201) than in the patients with CAD (n=201). The odds ratio of the TC + TT versus CC genotype of the C242T polymorphism between control subjects and case patients was 0.49 (95% CI, 0.28 to 0.87) (P=.015). The prevalence of the genotypes of the A640G polymorphism was not different between groups. The association of C242T polymorphism of the p22 phox gene with CAD was statistically significant and independent of other risk factors.


The mutation of the potential heme-binding site of the p22 phox gene may reduce susceptibility to CAD. Our observations suggest that the C242T polymorphism of the p22 phox gene is a novel genetic marker that has a protective effect on coronary risk.

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