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Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians.

ABSTRACT: Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6.We conducted a case-control study of AMI and GP6 in a community-based population (n = 652 cases, 625 controls). We also examined men and women separately and stratified the latter by use of hormone replacement therapy (HRT). Among both sexes, the strongest association was for a protective missense polymorphism (rs1163662) in the GP6 gene (OR = 0.70; Bonferroni-adjusted p < 0.05). SNPs in GP6 were also strongly associated with AMI among women who reported ever taking HRT, but not among women who never took HRT. Haplotype analyses were consistent with the single-SNP findings.In this sample of white non-Hispanic men and women, several SNPs in GP6 were significantly related to risk of AMI. Development of pharmacologic therapy directed towards platelet activity and thrombosis may reduce the incidence of AMI among at-risk groups.

SUBMITTER: Shaffer JR

PROVIDER: S-EPMC2888832 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians.

Shaffer J R JR Kammerer C M CM Dorn J J Ferrell R E RE Iacoviello L L Trevisan M M Donahue R P RP

Nutrition, metabolism, and cardiovascular diseases : NMCD 20100315 8

<h4>Background and aims</h4>Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6.<h4>Methods and results</h4>We conducted a case-control study of AMI and GP6 in a community-based population (n = 652 cases, 625 controls) ...[more]

PMID: 20227257

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Project description:The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E1 for detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T>C; rs2046934), P2Y12 (34C>T; rs6785930), COX-1 (-842A>G; rs10306114), GPVI (13254T>C; rs1613662), and GPIbA (5T>C; rs2243093) polymorphisms, DNA of patients with AIM was tested by real-time-polymerase chain reaction and melting curve analysis using the LightCycler 480 analyzer (Roche Diagnostics).The cut-off points used for patients with effective ASA therapy are 25% of aggregated platelets and 220 area under the curve (AUC)/min if LTA or MEA, respectively. The cut-off points used for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively. Both LTA and MEA found that aspirin and thienopyridine therapies failed in 14.51% and 25.8%, respectively. The data were statistically processed using the SPSS version 15 software (SPSS, Inc.). Associations between receptor mutation status and response to therapy were assessed with Fisher's exact test. The significance level was set at 0.05.The aim of our work was to use the two functional laboratory methods described earlier to assess both aspirin and thienopyridine resistance and to determine the contribution of genetic polymorphisms of platelet receptors to resistance to antiplatelet therapy in AIM. Fisher's exact test showed a significant statistical correlation between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of COX1_A1 (-A842G). Fisher's exact test showed no statistically significant correlations between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of GP1bA (-5T>C) and GP6 (T13254C). Fisher's exact test showed no statistically significant correlation between mutational statuses of the receptors P2RY12 (i-T744C), P2RY12 (C34T), GP1bA (-5T>C), or GP6 (T13254C) and response to antiplatelet therapy with 75?mg of clopidogrel.

Dataset Information

Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians.

Publications

Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians.

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