The P2Y13 Met-158-Thr polymorphism, which is in linkage disequilibrium with the P2Y12 locus, is not associated with acute myocardial infarction

Abstract

Background and Aims. The aims of this study were to investigate (1) if P2Y12 polymorphisms defining the P2Y12 H2 allele are associated with any other SNPs that may explain the previously reported association with increased ADP induced platelet activation and association with peripheral arterial disease and coronary artery disease and (2) if such variants are associated with acute myocardial infarction (AMI) or classical risk factors for AMI. Methods and Results. The P2Y13 Met-158-Thr polymorphism was found to be in linkage disequilibrium (LD) with the P2Y12 H2 haplotype (all examined SNPs: D'= 1.0, r2=0.936-1.0), defining a novel P2Y12 H2/ P2Y13 Thr-158 haplotype. Genotyping of an AMI case control population (n= 1244 cases, 2488 controls) revealed no association of the P2Y13 Thr-158 allele with AMI (OR=0.96, 95% C.I. 0.82-1.12, P=0.63). Also, no differences between the genotype frequencies of P2Y13 Met-158-Met and Met-158-Thr/Thr-158-Thr were seen in AMI case-control subpopulations (early onset AMI OR=1.06, 95% CI. 0.85-1.31, P=0.62); family history of AMI (OR=0.98, 95%, C.I. 0.78-1.22, P=0.83) nor in early onset AMIs with family history of AMI (OR= 1.0, 95% C.I. 0.74-1.36, P= 1.0). Genotyping of the P2Y13 Met-158-Thr polymorphism in a population based sample (n=6055) revealed no association with cardiovascular risk factors. In addition, the P2Y13 Met-158-Thr polymorphism was genotyped in a diabetes case-control population, and associations were found neither with DM nor with any examined DM risk factors. Conclusion Genotyping. The P2Y13 Met-158-Thr polymorphism is in tight LD with the P2Y12 locus but is not associated with AMI or classical cardiovascular risk factors. © 2008 Amisten et al.