title: Effect of P2Y1 and P2Y12 genetic polymorphisms on the ADP-induced platelet aggregation in a Korean population.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Kyoung-Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Wan-Geun
authors.initials: WG
authors.lastname: Song
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Lee
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Joo
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000328:Adult; D000483:Alleles; D005838:Genotype; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics* / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics* / Q000378:metabolism; D056910:Republic of Korea; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate
keywords: ADP; P2Y(1); P2Y(12); Platelet aggregation; Polymorphism