GPla Polymorphisms Are Associated with Outcomes in Patients at High Cardiovascular Risk.

Dominik Rath,Meinrad Gawaz,Stefan Winter,Harald F Langer,Tobias Geisler,Matthias Schwab,Semjon Levertov,Fabian Stimpfle,Elke Schaeffeler,Michal Droppa,Karin Müller

doi:10.3389/fcvm.2017.00052

Abstract

Platelet membrane glycoprotein receptors mediate thrombus formation. GP Ia/IIa is an essential platelet integrin receptor. Single-nucleotide polymorphisms (SNPs) of the GP Ia/IIa gene alter GP Ia/IIa expression; however, their influence on cardiovascular disease remains unclear. This study aimed to investigate the effect of the GP Ia/IIa SNPs rs1126643 and rs1062535 on clinical outcomes in a large collective including high-risk patients with cardiovascular disease. GP Ia SNP analysis was performed in 943 patients with symptomatic coronary artery disease. All patients were tracked for all-cause death, myocardial infarction, and ischemic stroke for 360 days. Homozygous carriers of the minor allele showed significantly worse event-free survival when compared with major allele carriers in the complete collective as well as in the subset of high-risk patients (carrying all of the following three risk factors: diabetes type II, hypertension, and hyperlipidemia). There was no significant difference in the subset of low-risk patients (carrying none of the three risk factors). GPla SNPs are associated with cardiovascular prognosis especially in high-risk patients. Identification of GPIa SNPs is of importance to tailor therapies in patients at already high cardiovascular risk.

Highlights

Platelet membrane glycoprotein receptors (GP) mediate thrombus formation leading to generation of platelet thrombi that are involved in the development of acute ischemic events such as acute coronary syndrome (ACS) and ischemic stroke [1, 2]
The integrin, alpha 2 gene (ITGA2), which is coding for GP Ia/IIa, is located on chromosome 5q23-31
Rs1126643 was significantly correlated with the combined endpoint (CE) in patients who suffered from diabetes type II, arterial hypertension, and hyperlipidemia, but not in patients without any of these risk factors

Summary

Introduction

Platelet membrane glycoprotein receptors (GP) mediate thrombus formation leading to generation of platelet thrombi that are involved in the development of acute ischemic events such as acute coronary syndrome (ACS) and ischemic stroke [1, 2]. Among the essential platelet integrin receptors is GP Ia/IIa ( known as integrin α2β1). A single-nucleotide polymorphism (SNP) of the ITAG2 gene, that alters GP Ia/IIa expression, has been identified as GPla. Platelet membrane glycoprotein receptors mediate thrombus formation. GP Ia/IIa is an essential platelet integrin receptor. Single-nucleotide polymorphisms (SNPs) of the GP Ia/IIa gene alter GP Ia/IIa expression; their influence on cardiovascular disease remains unclear. This study aimed to investigate the effect of the GP Ia/IIa SNPs rs1126643 and rs1062535 on clinical outcomes in a large collective including high-risk patients with cardiovascular disease

Objectives

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Conclusion