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- Title
PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population.
- Authors
Wen-Yi Yang; Petit, Thibault; Cauwenberghs, Nicholas; Zhen-Yu Zhang; Chang-Sheng Sheng; Thijs, Lutgarde; Salvi, Erika; Izzi, Benedetta; Vandenbriele, Christophe; Fang-Fei Wei; Yu-Mei Gu; Jacobs, Lotte; Citterio, Lorena; Delli Carpini, Simona; Barlassina, Cristina; Cusi, Daniele; Hoylaerts, Marc F.; Verhamme, Peter; Kuznetsova, Tatiana; Staessen, Jan A.
- Abstract
Background: Platelet Endothelial Aggregation Receptor 1 (PEAR1), a membrane protein highly expressed in platelets and endothelial cells, plays a role in platelet contact-induced activation, sustained platelet aggregation and endothelial function. Previous reports implicate PEAR1 rs12041331 as a variant influencing risk in patients with coronary heart disease. We investigated whether genetic variation in PEAR1 predicts cardiovascular outcome in a white population. Methods: In 1938 participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes (51.3% women; mean age 43.6 years), we genotyped 9 tagging SNPs in PEAR1, measured baseline cardiovascular risk factors, and recorded Cardiovascular disease incidence. For SNPs, we contrasted cardiovascular disease incidence of minorallele heterozygotes and homozygotes (variant) vs. major-allele homozygotes (reference) and for haplotypes carriers vs. non-carriers. In adjusted analyses, we accounted for family clusters and baseline covariables, including sex, age, body mass index, mean arterial pressure, the total-to-HDL cholesterol ratio, smoking and drinking, antihypertensive drug treatment, and history of cardiovascular disease and diabetes mellitus. Results: Over a median follow-up of 15.3 years, 238 died and 181 experienced a major cardiovascular endpoint. The multivariable-adjusted hazard ratios of eight PEAR1 SNPs, including rs12566888, ranged from 0.87 to 1.07 (P ≥0.35) and from 0.78 to 1.30 (P ≥0.15), respectively. The hazard ratios of three haplotypes with frequency ≥10% ranged from 0.93 to 1.11 (P ≥0.49) for mortality and from 0.84 to 1.03 (P ≥0.29) for a cardiovascular complications. These results were not influenced by intake of antiplatelet drugs, nonsteroidal anti-inflammatory drugs, or both (P-values for interaction ≥ 0.056). Conclusions: In a White population, we could not replicate previous reports from experimental studies or obtained in patients suggesting that PEAR1 might be a susceptibility gene for cardiovascular complications.
- Subjects
BLOOD platelet aggregation; MEMBRANE proteins; ENDOTHELIAL cells; CARDIOVASCULAR diseases; HUMAN genetic variation; MEDICAL genetics
- Publication
BMC Medical Genetics, 2017, Vol 18, p1
- ISSN
1471-2350
- Publication type
Article
- DOI
10.1186/s12881-017-0411-x