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Arteriosclerosis, Thrombosis, and Vascular Biology
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on January 31, 2008

Arteriosclerosis, Thrombosis, and Vascular Biology. 2008
Published online before print January 31, 2008, doi: 10.1161/ATVBAHA.107.154823
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Submitted on August 29, 2007
Accepted on January 23, 2008

C242T Polymorphism of NADPH Oxidase p22phox and Recurrence of Cardiovascular Events in Coronary Artery Disease

Marcello Arca ; Beatrice Conti ; Anna Montali ; Pasquale Pignatelli ; Filomena Campagna ; Francesco Barillà ; Gaetano Tanzilli ; Roberto Verna ; Annarita Vestri ; Carlo Gaudio ; and Francesco Violi *

From the Department of Clinical and Medical Therapy (M.A., B.C., A.M., F.C.), Unit of Medical Therapy, the Department of the Heart and Great Vessels (F.B., G.T., C.G.) Attilio Reale, the Department of Experimental Medicine (P.P., R.V., A.V., F.V.), and Research Center for Clinical Trials (CRISC) (R.V., A.V.), La Sapienza University, Rome, Italy.

* To whom correspondence should be addressed. E-mail: Francesco.violi{at}uniroma1.it.

Objectives—The common C242T polymorphism in the gene for the p22phox subunit of NADPH oxidase has been reported to be negatively associated with oxidative stress, but whether it confers prognostic information is not yet clear.

Methods and Results—The incidence of major adverse cardiovascular events (MACE) were determined in 237 patients with coronary stenosis during a median follow-up of 7.8 years. The p22phox genotypes were evaluated in 213 patients (89.9%) by polymerase chain reaction and RsaI. digestion Plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, were also measured. In the univariate analysis, patients with CT/TT genotypes showed reduced recurrence of cardiovascular deaths, nonfatal MI, and revascularization procedures compared with homozygous carriers of the C allele. After controlling for confounders, a significantly lower risk of new revascularization procedures (HR=0.31, 95% CI 0.12 to 0.70; P=0.014) remained associated with the T allele. The Kaplan–Meier analysis showed a longer survival free from fatal and nonfatal MI in carriers of T allele (P<0.001). The presence of the 242T allele was associated with significantly reduced plasma concentrations of 8-OHdG.

Conclusions—The 242T allele was a predictor of lower risk of recurrence of cardiovascular events in high-risk patients and was associated with reduced systemic oxidative stress.


Key words: NADPH oxidase • polymorphisms • oxidative markers • atherosclerosis • cardiovascular risk • follow-up study