PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population

BMC Medical Genetics

Research Article

Marc F. Hoylaerts¹  Benedetta Izzi¹  Peter Verhamme¹  Christophe Vandenbriele¹  Simona Delli Carpini²  Lorena Citterio²  Erika Salvi³  Cristina Barlassina³  Daniele Cusi³  Tatiana Kuznetsova⁴  Wen-Yi Yang⁴  Lotte Jacobs⁴  Fang-Fei Wei⁴  Lutgarde Thijs⁴  Yu-Mei Gu⁴  Zhen-Yu Zhang⁴  Chang-Sheng Sheng⁴  Nicholas Cauwenberghs⁴  Thibault Petit⁵  Jan A. Staessen⁶ 

[1] Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium;Division of Nephrology and Dialysis, IRCCS San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milan, Italy;Genomics and Bioinformatics Platform at Filarete Foundation, Department of Health Sciences and Graduate School of Nephrology, Division of Nephrology, San Paolo Hospital, University of Milan, Milan, Italy;Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences,, University of Leuven, Campus Sint Rafaël, Box 7001, Kapucijnenvoer 35, BE-3000, Leuven, Belgium;Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences,, University of Leuven, Campus Sint Rafaël, Box 7001, Kapucijnenvoer 35, BE-3000, Leuven, Belgium;Cardiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium;Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences,, University of Leuven, Campus Sint Rafaël, Box 7001, Kapucijnenvoer 35, BE-3000, Leuven, Belgium;R&D Group VitaK, Maastricht University, Maastricht, The Netherlands;

关键词: Clinical genetics;    Cardiovascular risk;    PEAR1;    Population science;    Replication research;   

DOI  :  10.1186/s12881-017-0411-x

 received in 2017-02-17, accepted in 2017-04-20,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPlatelet 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.MethodsIn 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 minor-allele 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.ResultsOver 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).ConclusionsIn 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.

【 授权许可】

CC BY   
© The Author(s). 2017