Polymorphisms in CYP450 Genes and the Therapeutic Effect of Atorvastatin on Ischemic Stroke: A Retrospective Cohort Study in Chinese Population

Purpose: Ischemic stroke (IS) is one of the most common neurologic diseases and is the main cause of death and disability in the Chinese population. This retrospective cohort study was performed to elucidate the relationship between single nucleotide polymorphisms (SNPs) in cytochrome P450 genes and the therapeutic effect of atorvastatin. Methods: A total of 192 cases of IS were enrolled in the study. All patients were treated with atorvastatin, and their lipid levels and proportions were measured. Six SNPs in 4 cytochrome P450 genes (CYP2C19, CYP2D6, CYP3A4, and CYP4F2) related to drug metabolism were selected to be genotyped and analyzed. Findings: Data were analyzed for 192 patients (sex, male/female, 122/70; mean age, 69.81 [9.35] years; Hypertension, 163[84.90%]; Cigarette smoking, 34 [17.71%]). Among the 192 patients with IS treated with atorvastatin, it was found that the G allele of rs1065852 (CYP2D6) had a better effect on lowering of Delta LDL (P < 0.001), Delta LDL/LDL (P < 0.001), Delta(LDL/HDL) (P < 0.001), and Delta(LDL/HDL)/(LDL/ HDL) (P < 0.001). We also found that rs2242480 (CYP3A4) showed marginal association with Delta LDL (P = 0.049) under the dominant model. In addition, rs2242480 and rs1065852 exhibited cumulative effects on the lipid-lowering (Delta LDL, Delta LDL/LDL, and Delta[LDL/HDL]) efficacy of atorvastatin (P < 0.001). (C) 2018 Elsevier HS Journals, Inc. All rights reserved.