From the First Department of Internal Medicine, Kobe University School of
Medicine, Japan.
Correspondence to Seinosuke Kawashima, MD, The First Department of Internal Medicine, Kobe University School of Medicine, 7–5-1 Kusunoki-cho, Chuo-Ku, Kobe 650, Japan.
Background—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.
Methods and Results—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.
Conclusions—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.
© 1998 American Heart Association, Inc.
Brief Rapid Communications
Polymorphism of the NADH/NADPH Oxidase p22 phox Gene in Patients With Coronary Artery Disease
Key Words: coronary disease • genes • risk factors • free radicals • stress
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