Abstract 183: Genetic Determinants of CD39 Expression and Platelet Aggregation
Introduction: CD39 is an ATP and ADP hydrolyzing ectonucleotidase found on the endothelium, leukocytes and platelets. Prior work has shown that the genotype at the single nucleotide polymorphism rs10748643 correlates with CD39 expression (GG:high, AG:intermediate, AA: low) in lymphocytes. However the influence on CD39 expression in platelets is unresolved.
Objective: The aim of this study was to determine whether the rs10748643 genotype associates with low-dose ADP-induced platelet aggregation ex vivo.
Methods: Whole blood was obtained from healthy volunteers not on aspirin (baseline) and then treated with aspirin for 14 days (81 mg). Serum thromboxane levels were also measured to demonstrate ASA adherence. Platelet rich plasma was generated and platelet aggregation in response to 2.5 uM ADP was measured. DNA from whole blood was isolated and used for genotyping at rs10748643 by the Vanderbilt DNA Resources Core.
Results: The study population included 65 subjects.Genotyping revealed 23 GG, 28 AG and 14 AA at rs10748643 subjects. There was no difference in age (Years: AA: 32.4±11.7, AG: 34.2±9.5, GG: 33.5±9.4; P=0.72) or sex (Male: AA: 57%, AG: 76%, GG: 60%; P=0.34). Stimulation of platelets from untreated subjects with 2.5 uM ADP showed no difference in the percent aggregation (AA: 77.8±7.05%; AG: 75.9±4.85%, GG: 78.7±4.31%; P=0.233). Following aspirin treatment there was a significant decrease in thromboxane levels (P<0.001 compared to baseline) and an expected significant decrease in the percent aggregation in all genotypes compared to the pre-treatment aggregation (P<0.001). Analysis of “on aspirin” platelet aggregation by genotype demonstrated a nonsignificant trend of lower aggregation in AA individuals compared to AG and GG individuals (AA: 46±3.37%; AG: 52.4±3.13, GG: 56.2±3.1; P=0.148).
Conclusions: These data suggests that the rs10748643 genotype does not associate with differences in platelet aggregation at baseline or following aspirin therapy. However, the small size of the cohort examined is a clear limitation of the study. The trend for lower aggregation in AA individuals on aspirin is intriguing and studies in a larger cohort will determine if there is significance of these findings.
Author Disclosures: J.M. Flynn: None. E.V. Haddad: None. J.H. Cleator: None. T. Novitskaya: None. J.A. Oates: None. O.G. Boutaud: None. R.J. Gumina: None.
- © 2015 by American Heart Association, Inc.