The effects of CES 1 A 2 and CYP 2 C 19 polymorphisms on responsiveness to clopidogrel and clinical outcomes among Chinese patients with acute ischemic stroke

Little research about genotype and clopidogrel response related to acute ischemic stroke has been published. The study evaluated the gene polymorphisms involved in the metabolic process affecting clopidogrel response and acute ischemic stroke clinical outcomes. We evaluated 191 non-cardioembolic ischemic stroke (NCIS) patients treated with clopidogrel. The platelet reactivity with clopidogrel treatment for 5 days was measured using thrombelastography platelet mapping assay. CES1A2 A (-816) C and CYP2C19*2/*3 were screened by the Ligase Detection Reaction. The primary endpoint was the composite of vascular death, stroke recurrence and myocardial infract. The associations between the genotype and the primary endpoint were evaluated. The rate of platelet inhibition in patients with homozygous (CC) of CES1A2 A (-816) C was significantly lower than that in heterozygous (AC) and wild-type genotype (AA) in co-dominant model (P = 0.021); similar result was observed for CYP2C19 loss of function (LOF) alleles carriers (P = 0.015). The risk of primary endpoint increased with the presence of the CES1A2 (recessive model) and CYP2C19 LOF alleles (dominant model) during the mean follow-up of 9.5 months (P = 0.023 and P = 0.028, respectively). The two gene polymorphisms were independent prognostic factors for clinical outcomes in the final multivariate Cox regression model. Both the CES1A2 and CYP2C19 polymorphisms may be associated with platelet reactivity with clopidogrel treatment and increased the risk of vascular events in Chinese patients.