A synergic effect between CYP2C19∗2, CYP2C19∗3 loss-of-function and CYP2C19∗17 gain-of-function alleles is associated with Clopidogrel resistance among Moroccan Acute Coronary Syndromes patients

Objective: The main objective of our study was to investigate the association of CYP2C19∗2 and CYP2C19∗3 loss-of-function and CYP2C19∗17 gain-of-function variants of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute Coronary Syndromes patients. Results: Our results showed the existence of a synergic effect between the three alleles, statistically very significant, on Clopidogrel resistance among the treated patients (P = 0.0033). For the three variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes were the most frequent among ACS patients (CYP2C19∗2: 82.76% GA and 10.35% AA; CYP2C19∗3: 76.67% GA and 18.33% AA; CYP2C19∗17: 66.67% CT and 18.66% TT). Allelic frequencies were 51.73% vs 48.27% (P < 0.001); 56.67% vs 43.33% (P < 0.001); and 52% vs 48% (P = 0.01) for the mutant and wild type alleles of the CYP2C19∗2, CYP2C19∗3 and CYP2C19∗17 variants respectively. Our results support a role of CYP2C19 gene variants as a potential marker of Clopidogrel response. Understanding the functional and clinical consequences of these variants may help for treating patients more effectively, they could be genetically screened and appropriate dose adjustments could be made on the basis of their CYP2C19 genotype.