Published Online
on December 8, 2003

A more recent version of this article appeared on December 16, 2003

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Submitted on September 11, 2003
Revised on October 28, 2003
Accepted on October 28, 2003

P2Y₁₂ H2 Haplotype Is Associated With Peripheral Arterial Disease. A Case-Control Study

Pierre Fontana MD, Pascale Gaussem , Martine Aiach , Jean-Noël Fiessinger , Joseph Emmerich ^*, and Jean-Luc Reny MD

From INSERM U.428 (P.F., P.G., M.A., J.-N.F., J.E., J.-L.R), Service d’Hématologie Biologique A (P.F., P.G., M.A.), and Service de Médecine Vasculaire (J.-N.F., J.E., J.-L.R.), Hôpital Européen Georges Pompidou et Université Paris V, Paris, France.

^* To whom correspondence should be addressed. E-mail: joseph.emmerich{at}egp.ap-hop-paris.fr.

Background--We recently described a gain-of-function haplotype, called H2, of the adenosine diphosphate (ADP) receptor P2Y₁₂ gene associated with increased ADP-induced platelet aggregation ex vivo in healthy volunteers. Because platelets play a key role in atherosclerosis and arterial thrombosis, we tested the possible link between the H2 haplotype and the risk of peripheral arterial disease (PAD) in a case-control study.

Methods and Results--We studied 184 consecutive male patients under 70 years of age with PAD and 330 age-matched control subjects free of symptomatic PAD and with no cardiovascular history. Mean age was 57.1±7.2 years (cases) and 56.7±7.6 years (control subjects). The H2 haplotype was more frequent in patients with PAD than in control subjects (30% and 21%, respectively; OR, 1.6; CI, 1.1 to 2.5; P=0.02 in univariate analysis). This association with PAD remained significant in multivariate regression analysis (OR, 2.3; CI, 1.4 to 3.9; P=0.002) after adjustment for diabetes, smoking, hypertension, hypercholesterolemia, and other selected platelet receptor gene polymorphisms.

Conclusions--These data point to a role of the H2 haplotype in atherosclerosis and raise the possibility of relative thienopyridine resistance in carriers of the P2Y₁₂ H2 haplotype.

Key words: atherosclerosis • arteries • platelets • thrombosis • peripheral vascular disease

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