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

Publication date: Available online 28 February 2018
Source:Clinical Therapeutics
Author(s): Chen Peng, Ying Ding, Xin Yi, Yupei Shen, Zhiqiang Dong, Limei Cao, Qiang Li, Haiyan Ren, Lin He, Daizhan Zhou, Xu Chen
PurposeIschemic 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.MethodsA 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.FindingsData 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 ΔLDL (P < 0.001), ΔLDL/LDL (P < 0.001), Δ(LDL/HDL) (P < 0.001), and Δ(LDL/HDL)/(LDL/HDL) (P < 0.001). We also found that rs2242480 (CYP3A4) showed marginal association with ΔLDL (P = 0.049) under the dominant model. In addition, rs2242480 and rs1065852 exhibited cumulative effects on the lipid-lowering (ΔLDL, ΔLDL/LDL, and Δ[LDL/HDL]) efficacy of atorvastatin (P < 0.001).ImplicationsThe results suggest that CYP2D6 and CYP3A4 affect treatment with atorvastatin in patients with IS.



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