Clopidogrel pharmacogenetics: Associations between genotype and stent thrombosis risk in patients with stent placement

Dual-antiplatelet treatment with aspirin and clopidogrel is the recommended therapy for prevention of stent thrombosis occurrence in patients with arterial revascularization interventions.1 The clopidogrel effect, however, is characterized by considerable interindividual variability2 that depends on both genetic3,4 and non-genetic5,6 factors. Clopidogrel, is substrate for the P-glycoprotein multidrug-resistant 1 (MDR1), encoded by ABCB1 gene.7 After absorption, clopidogrel bioactivation is mediated via cytochrome P450 (CYP) system. Numerous studies have provided compelling evidence that single nucleotide polymorphisms (SNPs) in CYP2C19 may affect clopidogrel response.3,8–10 In contrast, inconsistent evidence exist concerning the association between clopidogrel outcome and genetic variants within the ABCB1 gene11–13 as well as CYP1A2, CYP2B6 and CYP2C9, other enzymes involved in clopidogrel bioactivations.14–21 For example, one study showed that patients carrying ABCB1 3435TT genotype had high risk of stent thrombosis after clopidogrel treatment22 but other studies failed to confirm the association23,24 or even reported a worse outcome for patients carrying the opposite genotype.10 In this pilot study, we report the associations between SNPs, in ABCB1, CYP1A2, CYP2B6, CYP2C9 and CYP2C19 genes, alone and in combinations, with stent thrombosis in clopidogrel-treated patients undergoing arterial revascularization intervention.