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

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0411-x) contains supplementary material, which is available to authorized users.

Genetic Variation in PEAR1, Cardiovascular Outcomes and Effects of Aspirin in a Healthy Elderly Population

“…29 However, these results were not confirmed in a Flemish population, which reported no association with several different cardiovascular and cerebrovascular phenotypes when using rs12566888 as a proxy SNP for rs12041331 (R 2 = 0.99, D = 1.00 with each other). 30 These latter findings were consistent with a subsequent publication showing no association between PEAR1 rs12041331 and ischemic events in Chinese patients with an acute coronary syndrome treated with aspirin and clopidogrel (HR = 1.30, 95% CI 0.74-2.29, P = 0.07), although it should be noted that statistical power was likely quite low in this study given a limited sample size of 196 patients. 31 Most recently, Xu et al prospectively assessed rs12041331 in over 2,400 Chinese patients with acute coronary syndrome or stable coronary artery disease undergoing stent implantation and treated with aspirin and clopidogrel.…”

Comparative transcriptome analysis of mammary epithelial cells at different stages of lactation reveals wide differences in gene expression and pathways regulating milk synthesis between Jersey and Kashmiri cattle

“…In Kashmiri cattle, only three genes, SNORD50 , PEAR1 and TMEM232 , were amongst top DEG between lactation stages. The membrane protein, PEAR1 , shows specific expression in endothelial and platelets cells and plays significant roles in platelet activity and cardiovascular disease [46,47]. TMEM232 has been reported to be co-expressed with SLC25A46 and NAA1 0.…”

Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI

“…In our cohort, in patients who were homozygous major allele carriers of rs12566888, the primary endpoint occurred more frequently (IR of 7.8/100 PY vs. 2.2/100 PY in homozygous major allele carriers vs. minor allele carriers) but failed statistical significance in multivariate Cox proportional hazard regression analysis (Wald test P = 0.122). A recently published study by Yang et al could also not replicate previous reports suggesting that SNP rs12566888 in PEAR1 might be a susceptibility gene for cardiovascular complications in Caucasians (Yang et al, 2017 ). Nevertheless, the individuals studied by Yang et al did not undergo PCI like our cohort and the fact that the primary endpoint failed to be significantly associated with rs12566888 in our study collective may also be due to its moderate sample size and possibly gender-specific effects.…”