TY - JOUR
T1 - PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population
AU - Yang, W.Y.
AU - Petit, T.
AU - Cauwenberghs, N.
AU - Zhang, Z.Y.
AU - Sheng, C.S.
AU - Thijs, L.
AU - Salvi, E.
AU - Izzi, B.
AU - Vandenbriele, C.
AU - Wei, F.F.
AU - Gu, Y.M.
AU - Jacobs, L.
AU - Citterio, L.
AU - Carpini, S.D.
AU - Barlassina, C.
AU - Cusi, D.
AU - Hoylaerts, M.F.
AU - Verhamme, P.
AU - Kuznetsova, T.
AU - Staessen, J.A.
PY - 2017/4/27
Y1 - 2017/4/27
N2 - 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.
AB - 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.
KW - Clinical genetics
KW - Cardiovascular risk
KW - PEAR1
KW - Population science
KW - Replication research
KW - ENDOTHELIAL AGGREGATION RECEPTOR-1
KW - GENOME-WIDE ASSOCIATION
KW - PLATELET-AGGREGATION
KW - IDENTIFICATION
KW - POLYMORPHISMS
KW - AGGREGABILITY
KW - CLOPIDOGREL
KW - ACTIVATION
KW - RESISTANCE
KW - OUTCOMES
U2 - 10.1186/s12881-017-0411-x
DO - 10.1186/s12881-017-0411-x
M3 - Article
SN - 1471-2350
VL - 18
JO - BMC Medical Genetics
JF - BMC Medical Genetics
IS - 1
M1 - 45
ER -