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.
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Authors | Su-Jun Lee, Il-Sun Jung, Eun-Ji Jung, Ji-Yeop Choi, Chang-Woo Yeo, Doo-Yeoun Cho, Yang-Weon Kim, Sang-Seop Lee, Jae-Gook Shin |
Journal | Thrombosis research
(Thromb Res)
Vol. 127
Issue 3
Pg. 220-7
(Mar 2011)
ISSN: 1879-2472 [Electronic] United States |
PMID | 21216445
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Elsevier Ltd. All rights reserved. |
Chemical References |
- P2RY12 protein, human
- Receptors, Purinergic P2Y12
- Adenosine Diphosphate
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Topics |
- Adenosine Diphosphate
(metabolism)
- Adult
- Haplotypes
- Humans
- Korea
- Linkage Disequilibrium
- Male
- Platelet Aggregation
- Polymorphism, Single Nucleotide
- Receptors, Purinergic P2Y12
(genetics)
- Young Adult
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