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Identification of P2Y12 single-nucleotide polymorphisms and their influences on the variation in ADP-induced platelet aggregation.

Authors
Lee, SJ; Jung, IS; Jung, EJ; Choi, JY; Yeo, CW; Cho, DY; Kim, YW; Lee, SS; Shin, JG
Citation
Thrombosis research, 127(3):220-227, 2011
Journal Title
Thrombosis research
ISSN
0049-38481879-2472
Abstract
INTRODUCTION: 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.



MATERIALS AND 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.
MeSH terms
Adenosine Diphosphate/*metabolismAdultHaplotypesHumansKoreaLinkage DisequilibriumMale*Platelet Aggregation*Polymorphism, Single NucleotideReceptors, Purinergic P2Y12/*geneticsYoung Adult
DOI
10.1016/j.thromres.2010.11.023
PMID
21216445
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Journal Papers > School of Medicine / Graduate School of Medicine > Family Practice & Community Health
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