P2Y12 H2 haplotype is associated with peripheral arterial disease: a case-control study.
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.


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.
Fontana
Pierre
P
INSERM U.428, Hôpital Européen Georges Pompidou et Université Paris V, Paris, France.
Gaussem
Pascale
P
Aiach
Martine
M
Fiessinger
Jean-Noël
JN
Emmerich
Joseph
J
Reny
Jean-Luc
JL
D000368:Aged; D001161:Arteriosclerosis / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12
D008565:Membrane Proteins; C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12