Platelet receptor P2RY12 haplotypes predict restenosis after percutaneous coronary interventions.
The platelet receptor P2Y12 (gene symbol P2RY12) is involved in several processes that contribute to restenosis after percutaneous coronary interventions (PCI). Therefore, common variation in the P2Y12 gene may serve as a useful marker for risk stratification. We studied whether common variation in the platelet receptor P2Y12 gene affects the risk of restenosis after PCI. Comprehensive coverage of common variation in the P2Y12 gene was obtained by genotyping five haplotype-tagging SNPs (ht-SNPs) in 2,062 PCI-treated patients who received a stent and participated in the GENetic DEterminants of Restenosis (GENDER) Study. Haplotypes were inferred and their association with target vessel revascularization (TVR) was studied. Seven P2Y12 haplotypes were identified with an allelic frequency above 5% (designated here H1 to H7) of which two (H5 and H7) were associated with a higher risk of TVR (hazard ratios [HR]=1.4, 95% confidence interval [CI]=1.0-2.0; and HR=1.6, 95% CI=1.2-2.0, respectively) than the reference P2Y12 haplotype (H1), which contains the common alleles of all five P2Y12 ht-SNPs. Our study shows that common variation in the P2Y12 gene predicts restenosis in PCI-treated patients.
Rudez
Goran
G
Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Pons
Douwe
D
Leebeek
Frank
F
Monraats
Pascalle
P
Schrevel
Marlies
M
Zwinderman
Aeilko
A
de Winter
Robbert
R
Tio
René
R
Doevendans
Pieter
P
Jukema
Wouter
W
de Maat
Moniek
M
D000368:Aged; D000483:Alleles; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D023903:Coronary Restenosis / Q000097:blood / Q000209:etiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12; D012307:Risk Factors; D015607:Stents
C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12