INTRODUCTION: Carriage of CYP2C19*2 allele is associated with diminished platelet response to clopidogrel. However, the loss-of-function impact of CYP2C19*3 allele on antiplatelet effect of clopidogrel has not been definitely verified. We conducted this study to compare decreased response to clopidogrel according to carriage of CYP2C19*2 vs. *3 allele. MATERIALS AND METHODS: The study included 190 consecutive Korean patients undergoing elective percutaneous coronary intervention. Light transmittance aggregometry and the VerifyNow P2Y(12) assay were used to assess platelet reactivity (PR) at least 12 hours after 300-mg loading of clopidogrel. The cutoff of high on-treatment PR (HPR) was defined as 5 μmol/L ADP-induced PR >50%. CYP2C19 genotype was analyzed by the SNaPshot method. RESULTS: Carriers of at least one CYP2C19 variant allele were 115 patients (60.5%), and allelic frequency of CYP2C19*2 and *3 was 30.3% and 6.8%, respectively. PR and the rate of HPR increased proportionally according to the number of CYP2C19 variant allele. Carriage of CYP2C19 variant allele was an only independent predictor of HPR in multivariate analysis. When we compare the effect of allelic carriage, there were no significant differences in platelet measures and the rate of HPR between carriers of CYP2C19*2 and/or *3 allele(s) whether they were intermediate or poor metabolizers. CONCLUSION: Carriage of CYP2C19*3 allele is associated with diminished antiplatelet effect of clopidogrel, which may be as potent as the loss-of-function effect of CYP2C19*2 allele.
INTRODUCTION: Carriage of CYP2C19*2 allele is associated with diminished platelet response to clopidogrel. However, the loss-of-function impact of CYP2C19*3 allele on antiplatelet effect of clopidogrel has not been definitely verified. We conducted this study to compare decreased response to clopidogrel according to carriage of CYP2C19*2 vs. *3 allele. MATERIALS AND METHODS: The study included 190 consecutive Korean patients undergoing elective percutaneous coronary intervention. Light transmittance aggregometry and the VerifyNow P2Y(12) assay were used to assess platelet reactivity (PR) at least 12 hours after 300-mg loading of clopidogrel. The cutoff of high on-treatment PR (HPR) was defined as 5 μmol/L ADP-induced PR >50%. CYP2C19 genotype was analyzed by the SNaPshot method. RESULTS: Carriers of at least one CYP2C19 variant allele were 115 patients (60.5%), and allelic frequency of CYP2C19*2 and *3 was 30.3% and 6.8%, respectively. PR and the rate of HPR increased proportionally according to the number of CYP2C19 variant allele. Carriage of CYP2C19 variant allele was an only independent predictor of HPR in multivariate analysis. When we compare the effect of allelic carriage, there were no significant differences in platelet measures and the rate of HPR between carriers of CYP2C19*2 and/or *3 allele(s) whether they were intermediate or poor metabolizers. CONCLUSION: Carriage of CYP2C19*3 allele is associated with diminished antiplatelet effect of clopidogrel, which may be as potent as the loss-of-function effect of CYP2C19*2 allele.
Authors: J A Johnson; L H Cavallari; A L Beitelshees; J P Lewis; A R Shuldiner; D M Roden Journal: Clin Pharmacol Ther Date: 2011-09-14 Impact factor: 6.875