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ZJUS-B
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology)  2017, Vol. 18 Issue (1): 37-47    DOI: 10.1631/jzus.B1600333
Articles     
Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity
Xiao-yan Nie, Jun-lei Li, Yong Zhang, Yang Xu, Xue-li Yang, Yu Fu, Guang-kai Liang, Yun Lu, Jian Liu, Lu-wen Shi
School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Cardiology, Peking University People's Hospital, Beijing 100044, China; School of Public Health, Peking University Health Science Center, Beijing 100191, China; Department of Epidemiology, Fuwai Hospital, Beijing 100037, China; Department of Pharmacy, Hennepin County Medical Center, Minneapolis, Minnesota 55415, USA
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Abstract  Objective: To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG). Methods: One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs (*2,*3,*17) were genotyped and possible haplotypes were analyzed. Results: The high on-treatment platelet reactivity (HTPR) prevalence defined by a platelet inhibition rate <30% by TEG in adenosine diphosphate (ADP)-channel was 69 (38.33%). Six common haplotypes were inferred from four of the selected P2RY12 SNPs (denoted H0 to H5) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H1 showed a significantly lower incidence of HTPR than the reference haplotype (H0) in the total study population while haplotypes H1 and H2 showed significantly lower incidences of HTPR than H0 in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR. Conclusions: The combination of common P2RY12 variations including regulatory regions rather than rs2046934 (T744C) that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

Key words： P2RY12      CYP2C19      Haplotype      Single nucleotide polymorphism (SNP)      Clopidogrel      Thromboelastography     
Received: 21 July 2016      Published: 03 January 2017
CLC:  R543.3  
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Xiao-yan Nie
Jian Liu
Lu-wen Shi
Jun-lei Li
Yong Zhang
Yang Xu
Xue-li Yang
Yu Fu
Guang-kai Liang
Yun Lu
Cite this article:

Xiao-yan Nie, Jun-lei Li, Yong Zhang, Yang Xu, Xue-li Yang, Yu Fu, Guang-kai Liang, Yun Lu, Jian Liu, Lu-wen Shi. Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology), 2017, 18(1): 37-47.

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http://www.zjujournals.com/xueshu/zjus-b/10.1631/jzus.B1600333     OR     http://www.zjujournals.com/xueshu/zjus-b/Y2017/V18/I1/37

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