Pannexin1 Single Nucleotide Polymorphism and Platelet Reactivity in a Cohort of Cardiovascular Patients.

Jean-Luc Reny,Filippo Molica,Pierre Fontana,Florian B. Stierlin,Brenda R. Kwak

doi:10.1080/15419061.2017.1282469

Jean-Luc Reny, Filippo Molica

Open Access

https://doi.org/10.1080/15419061.2017.1282469

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Abstract

Pannexin1 (Panx1), a membrane channel-forming protein permitting the passage of small-sized molecules, such as ATP, is expressed in human platelets. Recently, we showed that inhibiting Panx1 affects collagen-induced platelet aggregation but not aggregation triggered by other agonists. We also found that a single nucleotide polymorphism (SNP; rs1138800) in the Panx1 gene encoded for a gain-of-function channel (Panx1-400C) and was associated with enhanced collagen-induced platelet reactivity. Here, we assessed the association of this SNP with platelet reactivity in a cohort of 758 stable cardiovascular patients from the ADRIE study treated with aspirin and/or clopidogrel. We found that presence of the Panx1-400C allele was not associated with platelet reactivity in stable cardiovascular patients, irrespective of the platelet aggregation agonist used (collagen, ADP or arachidonic acid) or the anti-platelet drug regimen. Moreover, the Panx1-400A > C SNP did also not affect the re-occurrence of cardiac ischemic events in the same stable cardiovascular patient cohort.

Highlights

Given the risk of hemorrhagic events or recurrent ischemic events associated with the two most prescribed anti-platelet drugs (Creager 1998), many efforts are made to find new regulators of platelet function
We found that a single nucleotide polymorphism (SNP; rs1138800) in the Panx1 gene encoded for a gain-of-function channel (Panx1-400C) and was associated with enhanced collageninduced platelet reactivity
We found that presence of the Panx1-400C allele was not associated with platelet reactivity in stable cardiovascular patients, irrespective of the platelet aggregation agonist used or the anti-platelet drug regimen

Summary

Introduction

Given the risk of hemorrhagic events or recurrent ischemic events associated with the two most prescribed anti-platelet drugs (aspirin and clopidogrel) (Creager 1998), many efforts are made to find new regulators of platelet function. In this context, a new glycoprotein discovered in 2003 and called Pannexin (Panx1) has emerged as a potential target (Taylor et al 2014; Molica et al 2015). Given the crucial role of ATP and ADP in platelet function, Panx may play a role in platelet aggregation

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