Genetic variations in PEAR1 are associated with progression of coronary artery disease

Abstract Aim Platelet endothelial aggregation receptor 1 (PEAR1) is a newly discovered membrane protein mainly expressed in endothelial cells and platelets. Previous researches have indicated the effect PEAR1 had on inflammation. This study aims to investigate the association between PEAR1 genetic variations and coronary artery disease (CAD) progression, which was regarded as a chronic inflammatory procedure. Methods We genotyped twelve common single nucleotide polymorphisms (SNPs) (rs2768759, rs2768762, rs12566888, rs12041331, rs11264579, rs77235035, rs57731889, rs822441, rs822442, rs11264581, rs56260937, and rs4661012) and detected the DNA methylation level of fourteen CpG loci in the promoter of PEAR1 in 162 Chinese patients with CAD. We accessed the association between PEAR1 genetic variants and the progression status of CAD, separated into stable angina, unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Results This CAD cohort included 40 (24.7%) with stable angina, 85 (52.5%) with unstable angina, 33 (20.4%) with NSTEMI, and 4 (2.5%) with STEMI. After adjusting for age, sex, hyperlipidemia, and diabetes mellitus as covariates in multiple logistic regression, rs12041331 was the only SNP that significantly associated with CAD type. Carriers of the A allele in rs12041331 were more likely to develop an unstable state (RR=1.996, 95%CI=1.075~3.710, p-value=0.029, Fig. 1). Carriers of A allele in rs11264579 is a potential risk factor of progression of atherosclerosis (RR=2.84, 95%CI=0.99~8.10, p-value=0.051, Fig. 1). Compared with other sites, SNPs of intron 1 were more likely to be associated with the risk of atherosclerosis progression (Fig.2). Conclusion Carriers of A allele in rs12041331 may lead to an increased risk of CAD progression. Region-specific genetic variant reinforces the association between PEAR1 and the risk of atherosclerosis progression.Effect of PEAR1 genetic variants.Correlation between PEAR1 SNPs and risk.