Yang Wen-Yi, Petit Thibault, Cauwenberghs Nicholas, Zhang Zhen-Yu, Sheng Chang-Sheng, Thijs Lutgarde, Salvi Erika, Izzi Benedetta, Vandenbriele Christophe, Wei Fang-Fei, Gu Yu-Mei, Jacobs Lotte, Citterio Lorena, Delli Carpini Simona, Barlassina Cristina, Cusi Daniele, Hoylaerts Marc F, Verhamme Peter, Kuznetsova Tatiana, Staessen Jan A
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences,, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium.
Cardiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
BMC Med Genet. 2017 Apr 27;18(1):45. doi: 10.1186/s12881-017-0411-x.
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.
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 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.
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).
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.
血小板内皮聚集受体1（PEAR1）是一种在血小板和内皮细胞中高度表达的膜蛋白，在血小板接触诱导激活、持续血小板聚集和内皮功能中发挥作用。先前的报告表明PEAR1 rs12041331是影响冠心病患者风险的一个变异。我们调查了PEAR1基因变异是否能预测白种人群的心血管结局。
在参与佛兰德环境、基因与健康结局研究的1938名参与者中（51.3%为女性；平均年龄43.6岁），我们对PEAR1中的9个标签单核苷酸多态性（SNP）进行了基因分型，测量了基线心血管危险因素，并记录了心血管疾病发病率。对于SNP，我们对比了次要等位基因杂合子和纯合子（变异型）与主要等位基因纯合子（参照型）的心血管疾病发病率，以及单倍型携带者与非携带者的心血管疾病发病率。在调整分析中，我们考虑了家族聚类和基线协变量，包括性别、年龄、体重指数、平均动脉压、总胆固醇与高密度脂蛋白胆固醇比值、吸烟和饮酒、抗高血压药物治疗以及心血管疾病和糖尿病史。
在中位随访15.3年期间，238人死亡，181人经历了主要心血管终点事件。包括rs12566888在内的8个PEAR1 SNP的多变量调整风险比分别为0.87至1.07（P≥0.35）和0.78至1.30（P≥0.15）。频率≥10%的三种单倍型的死亡风险比为0.93至1.11（P≥0.49），心血管并发症风险比为0.84至1.03（P≥0.29）。这些结果不受抗血小板药物、非甾体抗炎药或两者联合使用的影响（交互作用P值≥0.056）。
在白种人群中，我们无法重复先前实验研究或在患者中获得的报告结果，即提示PEAR1可能是心血管并发症的易感基因。
