Abstract 19748: CD39-associated SNP and Secondary Cardiovascular Events

Abstract

Introduction: CD39 (ectonucleoside triphosphate diphosphohydrolase) is a nucleotidase expressed on endothelial cells, vascular smooth muscles cells, leukocytes, and platelets. CD39 plays a key role in vascular homeostasis, hydrolyzing extracellular ATP or ADP to AMP. Prior work has demonstrated that the genotype at the single nucleotide polymorphism (SNP) rs10748643 correlates with CD39 expression on HapMap lymphocytes (GG: high, GA: intermediate, AA: baseline). Hypothesis: The aim of this study was to determine if an association exists between the rs10748643 genotype and secondary cardiovascular events. Methods: Subjects treated with placement of an intracoronary stent and on clopidogrel therapy for coronary artery disease were identified in the BioVU DNA repository that links DNA to Synthetic Derivative, a de-identified electronic health record. Selection of the study population was based on a combination of ICD 9th edition, Current Procedural Terminology codes, laboratory values, and natural language processing in physician notes. “Case” or “control” status was assigned depending on recurrence of a secondary cardiovascular event (myocardial infarction, revascularization and/or death) within two years. Genotyping for rs10748643 was performed using TaqMan. Results: The study population included 189 cases and 379 controls, with comparable demographics. There were 47 MIs, 14 deaths, and 166 revascularizations. We compared the composite outcomes of MI and/or death or MI, death and/or revascularization. We found no difference in the composite end-point of MI, death and revascularization, however the GG-genotype at rs10748443 was associated with an increase in the composite end-point of MI and/or death (HR GG:AA: 3.82 95% CI 1.10 - 13.29; P=0.039). Conclusions: The GG genotype, was associated with an increased incidence of the composite end-point of myocardial infarction and death in patients who received intracoronary stents for coronary artery disease and were treated with clopidogrel. This is the first study to demonstrate an association of a CD39-associated SNP with human cardiac pathology. Confirmatory studies are underway in a larger cohort.