title: Identification of P2Y12 single-nucleotide polymorphisms and their influences on the variation in ADP-induced platelet aggregation.
abstract: BACKGROUND
  Although P2Y12 has a significant role in normal hemostasis and thrombosis, no genetic study has been described about the association between P2Y12 variants and the extent of ADP-induced platelet activation in the Korean population.
  
  
  METHODS
  The expression levels of two reference sequences of P2Y12 mRNA transcripts (variants 1 and 2) were examined in the whole blood before direct DNA sequencing. The subjects were screened for single-nucleotide polymorphisms (SNPs) in P2Y12 by direct DNA sequencing (n=50). Frequencies of P2Y12 single nucleotide polymorphisms (SNPs), linkage disequilibrium blocks, haplotype structures, and haplotype-tagging SNPs were determined. The effects of genetic variation in the P2Y12 gene on the extent of ADP-induced platelet aggregation were studied in healthy Korean men (n=40).
  
  
  RESULTS
  Variant 2 (NM 176876.1) was the predominantly expressed form in all subjects, but variant 1 was also weakly expressed in all cases (n=10). A total of 20 SNPs were identified: 2 in exons, 5 in introns, and 8 and 5 in the 5'-untranslated regions of the known P2Y12 RNA variants 1 and 2, respectively. Genetic analysis of the P2Y12 SNPs and haplotypes revealed a statistically significant association between P2Y12 haplotype, denoted H3, and an increase in the ADP-induced platelet aggregation response relative to that for the reference haplotype H1 (P=0.01).
  
  
  CONCLUSIONS
  Application of these findings to the development of a multivariate model might be useful in explaining the variable outcome of antiplatelet drug therapy in Asian populations.
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University Busan Paik Hospital, Inje University, Busan, South Korea.
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Il-Sun
authors.initials: IS
authors.lastname: Jung
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Jung
authors.forename: Ji-Yeop
authors.initials: JY
authors.lastname: Choi
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Yeo
authors.forename: Doo-Yeoun
authors.initials: DY
authors.lastname: Cho
authors.forename: Yang-Weon
authors.initials: YW
authors.lastname: Kim
authors.forename: Sang-Seop
authors.initials: SS
authors.lastname: Lee
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000328:Adult; D006239:Haplotypes; D006801:Humans; D007723:Korea; D015810:Linkage Disequilibrium; D008297:Male; D010974:Platelet Aggregation; D020641:Polymorphism, Single Nucleotide; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D055815:Young Adult
chemical_list: C548576:P2RY12 protein, human; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate