Effect of P2Y1 and P2Y12 genetic polymorphisms on the ADP-induced platelet aggregation in a Korean population.

BACKGROUND

P2Y1 and P2Y12 receptors are expressed in platelet membranes and are involved in ADP-induced platelet aggregation. Genetic polymorphisms of P2Y1 and P2Y12 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 P2Y1 and P2Y12 genetic polymorphisms in a Korean population and to assess their role in ADP (5 μmol/L)-induced maximal platelet aggregation.

METHODS

P2Y1 (c.1622A>G) and P2Y12 (i-139C>T, i-744T>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 P2Y1 and P2Y12 were as follows: 0.3101 for P2Y1 c.1622A>G; 0.1804 for P2Y12 i-139C>T, 0.1804 for i-744T>C, 0.1804 for i-801insA, 0.1266 for P2Y12 c.52G>T, and 0.2658 for P2Y12 c.34C>T. ADP-induced maximal platelet aggregation was not influenced by the P2Y1 c.1622A>G polymorphism and was also not affected by three intronic P2Y12 polymorphisms and the P2Y12 c.34C>T polymorphism. However, the P2Y12 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 P2Y1 and P2Y12 genes were very polymorphic in a Korean population. Three intronic P2Y12 polymorphisms (i-139C>T, i-744T>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 P2Y1 c.1622A>T polymorphism.