title: CYP2C19 polymorphism and antiplatelet effects of clopidogrel in Chinese stroke patients.
abstract: Recently published data indicate that CYP2C19*2 allele is the major determinant of metabolic bioactivation of clopidogrel and thereby variability of antiplatelet effect of clopidogrel in white or black patients undergoing elective coronary stent placement. The conclusion may not be fully generalized or extrapolated to the Chinese people due to significantly higher frequencies of the CYP2C19*2 or *3 variant alleles. We sought to investigate whether the CYP2C19*2 or *3 alleles affects platelet reactivity of clopidogrel in Chinese stroke patients. The study included 183 consecutive Chinese stroke patients after loading with clopidogrel 300 mg. Platelet function was assessed by adenosine diphosphate-induced (ADP 20 micromol/L) platelet aggregation and by light transmittance aggregometry (LTA) after seven 75-mg maintenance doses of clopidogrel before discharge. CYP2C19*2 or *3 genotypes were determined by time-of-flight mass spectrometer (MALDI/TOF-MS). In those patients who were carriers of 1 mutant allele (mutant heterozygotes, CYP2C19*1/*2 or *1/*3), ADP-induced maximum platelet aggregation (MPA) were significantly different compared with wild-type homozygous patients [37.2% (IQR, 19.6 to 50.5%) versus 23.6% (IQR, 14.0 to 35.4%), respectively; P=0.002]. In addition, in the patients who were carriers of 2 mutant allele (mutant homozygotes, CYP2C19*2/*2, *2/*3 or *3/*3,), MPA were also significantly different compared with wildtype homozygous patients [35.7% (IQR, 21.0 to 78.1%) versus 23.6% (IQR, 14.0 to 35.4%, respectively; P = 0.039]. By multivariable linear regression, CYP2C19*2 or *3 loss-of-function alleles were independently associated with ADP-induced MPA measurements (partial R2 = 0.138, P = 0.001). CYP2C19*2 or *3 allele does link to increased MPA and clopidogrel response.
authors.affiliation: Department of Neurology, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Hong-Dong
authors.initials: HD
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Tan
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Ding
authors.forename: Zhi-Qun
authors.initials: ZQ
authors.lastname: Gu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zou
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D000077144:Clopidogrel; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020521:Stroke / Q000097:blood* / Q000188:drug therapy; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D004247:DNA; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine