Background: There have been few studies on CYP2C19  genotypes and clopidogrel response associated with ischemic stroke (IS), especially IS complicated by type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association between CYP2C19  polymorphisms and high on-treatment platelet reactivity (HTPR) in IS patients with T2DM in China.
Patients and Methods: A total of 426 consecutive IS patients with T2DM were enrolled in this case-control study and they were divided into HTPR group and non-HTPR group according to the ADP-induced platelet inhibition (PIADP) assessed by thromboelastography (TEG). Genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Various clinical and demographic data were also recorded. The association between CYP2C19  genetic variants and platelet function was assessed.
Results: Carriers of CYP2C19*2  heterozygous and mutant homozygous genotypes showed significantly lower PIADP than non-carriers (27.2% vs 38.3%, p < 0.001; 27.41% vs 38.3%, p = 0.012, respectively). Compared with the control group, the CYP2C19*2  A allele was more frequent in the HTPR group (34.51% vs 25.82%, p = 0.002). The carriage of CYP2C19*2  mutant allele was significantly associated with increased risk of HTPR (odds ratio (OR) = 1.94, 95% confidence interval (CI) = 1.32– 2.85). There was no significant correlation between CYP2C19*3  or *17  genotypes and HTPR risk.
Conclusion: CYP2C19*2  mutant allele was associated with attenuated platelet response to clopidogrel and increased risk of HTPR in IS patients with T2DM, suggesting that CYP2C19*2  polymorphism might be an important predictor of HTPR in this high-risk population.
Keywords: clopidogrel, ischemic stroke, type 2 diabetes mellitus, CYP2C19 , high on-treatment platelet reactivity