Diversity of platelet function and genetic polymorphism in clopidogrel-treated Chinese patients.
We investigated the correlation between genetic polymorphisms of cytochrome P450 enzyme genes and the outcome of clopidogrel treatment in 118 coronary disease patients after percutaneous coronary intervention at the Chinese PLA General Hospital. Patients were divided into an ischemia event relapse group (IERG) and a non-IERG group (NIERG) based on relapse of ischemia events within 6 months after percutaneous coronary intervention. Ischemia occurred in 26.27% of patients. Thromboelastogram platelet mapping results showed that compared with the NIERG, the ADP-induced platelet inhibition ratio in the IERG was significantly lower (31.33 ± 24.91% vs 54.68 ± 26.63%, P < 0.05). The platelet inhibition ratio of patients carrying mutant alleles CYP3A5*3 (41.98 ± 29.33% vs 52.89 ± 26.49%), CYP2C19*2 (43.15 ± 27.97% vs 55.89 ± 26.71%), and P2Y12*1 (38.74 ± 24.36% vs 52.19 ± 28.58%) was lower than patients with the wild-type alleles. The frequency of ischemia event relapse in patients with the mutant alleles CYP3A5*3 and CYP2C19*2 was significantly higher than patients carrying the G/G genotype; however, there was no significant difference between patients carrying the T/T genotype and C allele of P2Y12*1. Thus, coexisting polymorphisms of CYP3A5*3 and 2C19*2, but not P2Y12*1, play an important role in the variability of clopidogrel's curative effect.
Clinical Laboratory, The 309th Hospital of People's Liberation Army, Beijing, China.
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B
Sun
Clinical Laboratory, General Hospital of People's Liberation Army, Beijing, China.
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J
Li
Clinical Laboratory, The 309th Hospital of People's Liberation Army, Beijing, China.
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M
Dong
Clinical Laboratory, General Hospital of People's Liberation Army, Beijing, China.
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Yang
Clinical Laboratory, The 309th Hospital of People's Liberation Army, Beijing, China.
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C
Wu
Clinical Laboratory, The 309th Hospital of People's Liberation Army, Beijing, China.
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Zhu
Clinical Laboratory, General Hospital of People's Liberation Army, Beijing, China ylc301@126.com.
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YL
Cong
D000244:Adenosine Diphosphate / Q000737:chemistry; D000328:Adult; D000368:Aged; D000483:Alleles; D001777:Blood Coagulation; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002681:China; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007511:Ischemia / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062645:Percutaneous Coronary Intervention; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D012008:Recurrence; D013916:Thrombelastography; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D013988:Ticlopidine