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

WY Yang, T Petit, N Cauwenberghs, ZY Zhang, CS Sheng, L Thijs, Erika Salvi, B Izzi, C Vandenbriele, FF Wei, YM Gu, L Jacobs, L Citterio, S Delli Carpini, Cristina Barlassina, D Cusi, MF Hoylaerts, P Verhamme, T Kuznetsova, JA Staessen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 43.6years), 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 15.3years, 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. © 2017 The Author(s).
Original languageEnglish
Article number45
JournalBMC Medical Genetics
Volume18
Issue number16
DOIs
Publication statusPublished - 2017

Fingerprint

Platelet Aggregation
Cardiovascular Diseases
Population
Genes
Single Nucleotide Polymorphism
Homozygote
Haplotypes
Blood Platelets
Alleles
Platelet Aggregation Inhibitors
Incidence
Heterozygote
HDL Cholesterol
Antihypertensive Agents
Drinking
Coronary Disease
Diabetes Mellitus
Arterial Pressure
Membrane Proteins
Body Mass Index

Cite this

Yang, WY., Petit, T., Cauwenberghs, N., Zhang, ZY., Sheng, CS., Thijs, L., ... Staessen, JA. (2017). PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population. BMC Medical Genetics, 18(16), [45]. https://doi.org/10.1186/s12881-017-0411-x

PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population. / Yang, WY; Petit, T; Cauwenberghs, N; Zhang, ZY; Sheng, CS; Thijs, L; Salvi, Erika; Izzi, B; Vandenbriele, C; Wei, FF; Gu, YM; Jacobs, L; Citterio, L; Delli Carpini, S; Barlassina, Cristina; Cusi, D; Hoylaerts, MF; Verhamme, P; Kuznetsova, T; Staessen, JA.

In: BMC Medical Genetics, Vol. 18, No. 16, 45, 2017.

Research output: Contribution to journalArticle

Yang, WY, Petit, T, Cauwenberghs, N, Zhang, ZY, Sheng, CS, Thijs, L, Salvi, E, Izzi, B, Vandenbriele, C, Wei, FF, Gu, YM, Jacobs, L, Citterio, L, Delli Carpini, S, Barlassina, C, Cusi, D, Hoylaerts, MF, Verhamme, P, Kuznetsova, T & Staessen, JA 2017, 'PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population', BMC Medical Genetics, vol. 18, no. 16, 45. https://doi.org/10.1186/s12881-017-0411-x
Yang, WY ; Petit, T ; Cauwenberghs, N ; Zhang, ZY ; Sheng, CS ; Thijs, L ; Salvi, Erika ; Izzi, B ; Vandenbriele, C ; Wei, FF ; Gu, YM ; Jacobs, L ; Citterio, L ; Delli Carpini, S ; Barlassina, Cristina ; Cusi, D ; Hoylaerts, MF ; Verhamme, P ; Kuznetsova, T ; Staessen, JA. / PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population. In: BMC Medical Genetics. 2017 ; Vol. 18, No. 16.
@article{0cf5355962ca4d37bc6e9d2331c1141f,
title = "PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population",
abstract = "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 43.6years), 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 15.3years, 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. {\circledC} 2017 The Author(s).",
author = "WY Yang and T Petit and N Cauwenberghs and ZY Zhang and CS Sheng and L Thijs and Erika Salvi and B Izzi and C Vandenbriele and FF Wei and YM Gu and L Jacobs and L Citterio and {Delli Carpini}, S and Cristina Barlassina and D Cusi and MF Hoylaerts and P Verhamme and T Kuznetsova and JA Staessen",
year = "2017",
doi = "10.1186/s12881-017-0411-x",
language = "English",
volume = "18",
journal = "BMC Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central",
number = "16",

}

TY - JOUR

T1 - PEAR1 is not a major susceptibility gene for cardiovascular disease in a Flemish population

AU - Yang, WY

AU - Petit, T

AU - Cauwenberghs, N

AU - Zhang, ZY

AU - Sheng, CS

AU - Thijs, L

AU - Salvi, Erika

AU - Izzi, B

AU - Vandenbriele, C

AU - Wei, FF

AU - Gu, YM

AU - Jacobs, L

AU - Citterio, L

AU - Delli Carpini, S

AU - Barlassina, Cristina

AU - Cusi, D

AU - Hoylaerts, MF

AU - Verhamme, P

AU - Kuznetsova, T

AU - Staessen, JA

PY - 2017

Y1 - 2017

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 43.6years), 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 15.3years, 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. © 2017 The Author(s).

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 43.6years), 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 15.3years, 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. © 2017 The Author(s).

U2 - 10.1186/s12881-017-0411-x

DO - 10.1186/s12881-017-0411-x

M3 - Article

VL - 18

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

IS - 16

M1 - 45

ER -