Polymorphisms of MDR1, CYP2C19 and P2Y12 genes in Indian population: effects on clopidogrel response.

AIMS/OBJECTIVE: Influence of genetic variations on the response of clopidogrel, an antiplatelet drug is implicated. In the present study, the prevalence of single nucleotide polymorphisms of MDR1 (C3435T), CYP2C19 [CYP2C192 CYP2C193, CYP2C19*17] and P2Y12 (i-T744C) in Indian population and their effects on clopidogrel response was analyzed.

METHODS AND RESULTS

To analyze the prevalence of polymorphisms, 102 healthy individuals were recruited. Clopidogrel response was assessed by ADP induced platelet aggregation in clopidogrel naïve acute myocardial infarction (AMI) patients (n = 26) screened from 100 AMI cases, before loading dose of 300 mg, at 24 h before next dose and 6 days after on 75 mg per day and platelet aggregation inhibition (PAI) was calculated between these time intervals. Genotyping was carried out by PCR-based restriction enzyme digestion method for C3435T of MDR1 and i-T744C of P2Y12, by multiplex PCR for CYP2C192 (G681A) and CYP2C193 (G636A) and by nested PCR for CYP2C1917 (C806T). The effect of the above mentioned genetic variations on PAI was analyzed. Variant allele of CYP2C193 was not observed while the prevalence of 3435T of MDR1 (0.524), CYP2C192 (681A, 0.352); i-744C of P2Y12 (0.088), as well as wild type allele CYP2C1917 (C806, 0.897) associated with decrease clopidogrel response were observed. Trend toward poor response to clopidogrel was observed at 24 h with the variant genotypes of CYP2C19*2 and i-T744C of P2Y12 as compared to wild type.

CONCLUSION

The present study did show a trend toward impaired response of clopidogrel to inhibit platelet aggregation with variant genotypes of CYP2C19*2 and iT744C of P2Y12 compared to respective wild type genotype at 24 h.