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 thromboe- ...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 thromboe- lastography （TEG）. Methods： One hundred and eighty patients with acute coronary syndrome （ACS） treated with clopJdogrel and aspJdn were included and platelet function was assessed by TEG. Five selected P2RY12 single nu- cleotide 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 geno- typed 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 CYP2Clg 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.展开更多
基金Project supported by the Beijing Higher Education Young Elite Teacher Project(No.YETP0064),China
文摘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 thromboe- lastography （TEG）. Methods： One hundred and eighty patients with acute coronary syndrome （ACS） treated with clopJdogrel and aspJdn were included and platelet function was assessed by TEG. Five selected P2RY12 single nu- cleotide 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 geno- typed 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 CYP2Clg 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.
