Genetic polymorphism of CYP2C19 in recurrent ischemic stroke patients: prevalence and role in secondary prevention

Abstract Background Clopidogrel is widely used for secondary prevention of ischemic stroke (IS). Its effectiveness is significantly affected by genetic variations in the CYP2C19 gene. The occurrence and clinical implications of loss-of-function alleles (LoFA) within Egyptian populations remain underassessed. This study aimed to assess the prevalence of CYP2C19 LoFA in Egyptian IS patients, and their influence on clopidogrel effectiveness and the likelihood of recurrent IS. Results This prospective cohort study conducted in a tertiary stroke center included 182 consecutive acute IS patients. CYP2C19 genotypes were determined using TaqMan real-time PCR primers and probes. A total of 220 patients were enrolled; 182 completed follow-up. CYP2C19 *2 and *3 GA/AA genotypes were significantly associated with recurrent IS (OR 7.5; 95% CI 3.41–16.64 and OR 5.7;95% CI 2.49–13.17, respectively). In multivariable analysis adjusted for vascular risk factors, CYP2C19 LoFA remained independent predictors of recurrence (adjusted OR 5.62; 95% CI 1.85–27.40 and adjusted OR 4.08; 95% CI 1.41–21.59 for CYP2C19*2 and *3, respectively). Conclusions CYP2C19 LoFA are highly prevalent in Egyptian IS patients and were independently associated with clopidogrel non-response and recurrent stroke. Further large, multi-center studies should evaluate cost-effectiveness and long-term outcomes of personalized antiplatelet strategies in this population.