CYP2C19*2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome.
BACKGROUND
To investigate the contributions of CYP2C19 polymorphisms to the various clopidogrel responses tested by thrombelastography (TEG) in Chinese patients with the acute coronary syndrome (ACS).


METHODS
Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy. CYP2C19 loss of function (LOF) and gain of function (GOF) genotype, adenosine 5'-diphosphate (ADP)-channel platelet inhibition rate (PIR) tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients.


RESULTS
High on-treatment platelet reactivity (HTPR) prevalence defined by PIR <30% by TEG in ADP-channel was 32.76% (38/116). With respect to the normal wild type, CYP2C19*2, and *3 LOF alleles, and *17 GOF alleles, patients were classified into three metabolism phenotypes: 41.38% were extensive metabolizers (EMs), 56.90% were intermediate metabolizers (IMs), and 1.72% were poor metabolizers (PMs). Of the enrolled patients, 31.47%, 5.17%, and 0.43%, respectively, were carriers of *2, *3, and *17 alleles. The HTPR incidence differed significantly according to CYP2C19 genotypes, accounting for 18.75%, 41.54%, and 100.00% in EMs, IMs, and PMs, respectively. Eighteen (17.24%) ischemic events occurred during the 3-month follow-up, and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group.


CONCLUSIONS
Genetic CYP2C19 polymorphisms are relative to the inferior, the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.
Jian
J
Liu
Xiao-Yan
XY
Nie
Yong
Y
Zhang
Yun
Y
Lu
School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Lu-Wen
LW
Shi
Wei-Min
WM
Wang
D054058:Acute Coronary Syndrome / Q000235:genetics* / Q000503:physiopathology*; D000368:Aged; D000483:Alleles; D044466:Asian People; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D013916:Thrombelastography; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine