[PP.07.05] PLATELET ENDOTHELIAL AGGREGATION RECEPTOR 1 IS NOT A SUSCEPTIBILITY GENE FOR CARDIOVASCULAR DISEASE IN THE GENERAL POPULATION

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Abstract

Objective:

Platelet Endothelial Aggregation Receptor 1 (PEAR1), a membrane protein highly expressed in platelets and endothelial cells, mediates platelet contact-induced activation and sustained platelet aggregation. Among patients with coronary heart disease on antiplatelet agents, PEAR1 rs12041331 A allele carriers experienced more adverse cardiovascular outcomes and had higher death rates than GG homozygotes. We investigated whether in a white population genetic variation in PEAR1 predicts cardiovascular outcome.

Design and method:

Among 1938 participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes (51.3% women; mean age 43.6 years), we genotyped 9 SNPs and reconstructed haplotypes in PEAR1, measured baseline cardiovascular risk factors, and recorded fatal and non-fatal outcomes. For SNPs, we contrasted cardiovascular disease incidence of minor-allele heterozygotes and homozygotes (variant) vs. major-allele homozygotes (reference) and for haplotypes carriers vs. non-carriers.

Results:

Among these 1938 participants, 238 died and 182 experienced a major cardiovascular endpoint. In adjusted analyses, we accounted for baseline variables, including sex, age, body mass index, systolic pressure, the total-to-HDL cholesterol ratio, smoking and drinking, antihypertensive drug treatment and history of cardiovascular disease. The hazard ratios expressing the risk of death or of a cardiovascular endpoint in minor allele carriers vs. major allele homozygotes of 10 PEAR1 SNPs, including rs12041331, ranged from 0.95 to 1.03 (P > = 0.38) and from 0.72 to 1.36 (P > = 0.23), respectively. The multivariable-adjusted hazard ratios expressing the risk in carriers vs. non-carriers of three haplotypes with frequency > = 15% ranged from 0.89 to 1.09 (P > = 0.38) for mortality and from 0.67 to 1.26 (P > = 0.20) for a cardiovascular complications. These results were not influenced by intake of antiplatelet drugs, non-steroidal anti-inflammatory drugs, or both (P-values for interaction > = 0.27).

Conclusions:

In a white population, we could not replicate previous reports suggesting that PEAR1 might be a susceptibility gene for cardiovascular complications. Our findings were consistent irrespective of the use of antiplatelet agents.

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