Key result
PEAR1 genetic variation is not associated with cardiovascular events in a general White population.
Why the study?
Does genetic variation in PEAR1 predict cardiovascular outcome in a white population?
Cohort (n=1,938)
Does genetic variation in PEAR1 predict cardiovascular outcome in a white population?
Hazard Ratio: 0.78 (95% CI 0.5–1.2)
Absolute Event Rate: 4.76% vs 6.15%
p-value: p=0.25
Genetic variation in PEAR1 does not predict cardiovascular outcomes or mortality in a general White European population, challenging previous experimental and patient-specific findings.
PEAR1 variants do not predict CV events in general White populations; leaves open relevance in high-risk or non-European cohorts.
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 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. 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.
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Yang et al. (2017) conducted a cohort in Cardiovascular disease (n=1,938). PEAR1 genetic variation (rs12566888 T allele) vs. Major-allele homozygotes (GG) was evaluated on Cardiovascular events (HR 0.78, 95% CI 0.50-1.20, p=0.25). In a general White population, genetic variation in the PEAR1 gene, including the rs12566888 SNP, was not significantly associated with the incidence of cardiovascular events (HR 0.78).
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