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

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.

• 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)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• P2RY12 protein, human
• Receptors, Purinergic P2Y12
• Adenosine Diphosphate

Topics

• Adenosine Diphosphate (metabolism)
• Adult
• Haplotypes
• Humans
• Korea
• Linkage Disequilibrium
• Male
• Platelet Aggregation
• Polymorphism, Single Nucleotide
• Receptors, Purinergic P2Y12 (genetics)
• Young Adult