Cytochrome p-450 2c19 polymorphism and anti-aggregation effect of clopidogrel

Abstract

Clinical effect of clopidogrel depends on its biotransformation in human organism, made by several polymorphic enzymes, including CYP2C19. The polymorphic form CYP2C19*2 (681G>A) can cause reduced biotransformation of drug into an active metabolite. The objective of the study was to evaluate impact of patient’s CYP2C19 genotype on the clinical effect of clopidogrel. Materials and methods: The study includes 58 patients admitted to the treatment due to acute coronary syndrome. After two weeks treatment with clopidogrel (75 mg/day) platelet aggregation was measured by activation of platelets with 3.6 μmol/l of ADP and 4.5 μmol/l of epinephrine separately on optical aggregometer. Genotyping for CYP2C19 (681G>A) polymorphism was done by restriction fragment length polymorphism method. Results: Of the patients studied, 36 (62.07%) were CYP2C19 wild-type homozygotes (*1/*1) and 22 (37.93%) heterozygotes *1/*2. Into further study were included only 37 patients which regulary used clopidogrel within two weeks: 24 wild-type homozygotes (64.86%) and 13 heterozygotes *1/*2 (35.14%). Platelet aggregation induced by ADP was significantly higher (p=0.034) in CYP2C19*1/*2 allele carriers (mean 42.07%, SD 24.41) as compared to wild-type homozygotes (mean 28.04%, SD 14.49). There was no difference between aggregation of platelets induced by epinephrine in *1/*1 (mean 50.83%, SD 19.33) and *1/*2 (mean 48.77%, SD 24.98) allele carriers. Conclusion: Clinical effect of clopidogrel depends on the CYP2C19 genotype. CYP2C19*1/*1 carrier status is significantly associated with stronger anti-aggregation effect of clopidogrel. It emphasizes need of pharmacogenetic testing before clopidogrel prescription.