The influence of CYP2C19 polymorphisms on clopidogrel response in a multiethnic population with coronary artery disease

Clopidogrel plays a crucial role in preventing thrombotic events in patients undergoing percutaneous coronary intervention (PCI). CYP2C19 polymorphism involved in drug metabolism influence the antiplatelet efficacy of clopidogrel. Hence, this study aimed to determine the prevalence of CYP2C19 *2 (681G>A; rs4244285), *3 (636G>A; rs4986893) and *17 (-3402C>T; rs11188072 and -806C>T; rs12248560) alleles and their association with adenosine diphosphate – induced platelet aggregation (ADP-PA) in clopidogrel-treated multiethnic Malaysian patients (Chinese, Malay and non-Malay Bumiputras) before possible PCI. This study also aimed to assess the impact of CYP2C19 polymorphism with adverse clinical outcomes at one month and twelve months after hospital discharge in patients who had PCI. A total of 237 consecutive patients, who were electively admitted for possible PCI, were recruited from a Malaysian tertiary cardiology referral centre. These patients underwent either dual antiplatelet therapy, DAPT (clopidogrel plus aspirin) or aspirin monotherapy. CYP2C19 *2 (681G>A), *3 (636G>A) and *17 (-3402C>T) genotypes were determined by PCR-RFLP assay; while CYP2C19 *17 (-806C>T) genotype was detected by high resolution melt analysis. ADP-PA was assessed by Multiplate analyzer. Our study cohort had a mean age of 57.6 ± 11.1 years and 77.6% were male. The allelic frequencies of CYP2C19 *2, *3 and *17 variant alleles were 18.1%, 1.9%, and 0.4% for Chinese; 5.9%, 1.5% and 0.2% for Malay; 3.2%, 1.9% and 0.2% for native Iban; and 2.1%, 0.8% and 0.8% for other races respectively. The patients were categorized into three predicted metabolizers which were poor metabolizers (PMs), normal metabolizers (NMs) and ultrarapid metabolizers (UMs) according to the observed CYP2C19 genotypes. Majority of the PMs were Chinese followed by Malay, native Iban and other races. In this study, only 63.3% patients received DAPT. There was no significant difference in the post-treatment ADP-PA levels among the patients who received DAPT (p = 0.056). However, there was a significant difference in the post-treatment ADP-PA levels among the Chinese clopidogrel-treated patients (p = 0.031), but not among the other ethnic groups. From the 150 clopidogrel-treated patients, only 39.3% of the patients underwent PCI. Nevertheless, our study demonstrated that clinical outcomes were not significantly associated with clopidogrel antiplatelet therapy and CYP2C19 genotypes. In conclusion, CYP2C19 *2 carriers, but not CYP2C19 *3 and *17 carriers, were highly prevalent in Malaysians. Most of the CYP2C19 *2 variant allele carriers were Chinese patients. CYP2C19 polymorphism was not significantly associated with ADP-PA levels and clinical outcomes in those undergoing PCI in Malaysian population.