Effect of P2Y(1) and P2Y(12) genetic polymorphisms on the ADP-induced platelet aggregation in a Korean population

초록

Background: P2Y(1) and P2Y(12) receptors are expressed in platelet membranes and are involved in ADP-induced platelet aggregation. Genetic polymorphisms of P2Y(1) and P2Y(12) play a major role in the variation of ADP-induced platelet aggregation and in response in antiplatelet therapy. Objective: To evaluate the allele frequencies of P2Y(1) and P2Y(12) genetic polymorphisms in a Korean population and to assess their role in ADP (5 mu mol/L)-induced maximal platelet aggregation. Methods: P2Y(1) (c.1622A > G) and P2Y(12) (i-139C > T, i-744 T > C, i-ins801, c.52G > T, c.34C > T) polymorphisms were analyzed in 158 Korean healthy participants using pyrosequencing methods. Their ADP-induced maximal platelet aggregation was assessed by the turbidometric method. Results: The observed allele frequencies of P2Y(1) and P2Y(12) were as follows: 0.3101 for P2Y(1) c.1622A > G; 0.1804 for P2Y(12) i-139C > T, 0.1804 for i-744 T > C, 0.1804 for i-801insA, 0.1266 for P2Y(12) c.52G > T, and 0.2658 for P2Y(12) c.34C > T. ADP-induced maximal platelet aggregation was not influenced by the P2Y(1) c.1622A > G polymorphism and was also not affected by three intronic P2Y(12) polymorphisms and the P2Y(12) c.34C > T polymorphism. However, the P2Y(12) c.52G > T polymorphism caused a substantial difference in ADP-induced maximal platelet aggregation (62.75% for c.52GG, 66.27% for c.52GT, and 80.60% for c.52TT; P = 0.0092). Conclusions: The P2Y(1) and P2Y(12) genes were very polymorphic in a Korean population. Three intronic P2Y(12) polymorphisms (i-139C > T, i-744 T > C, i-801insA) were in complete linkage disequilibrium but not with the c.52C > T polymorphism in this population. Maximal platelet aggregation in response to ADP is associated with the c.52C > T polymorphism but not with the three intronic polymorphisms or the P2Y(1) c.1622A > T polymorphism. (c) 2013 Elsevier Ltd. All rights reserved.

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