SLCO1B1 and ABCB1 variants synergistically influence the atorvastatin treatment response in south Indian coronary artery disease patients: supplementary files

Introduction: Atorvastatin exhibits wide interindividual variability in treatment response, limiting the drug efficacy in coronary artery disease patients. Aim: To study the effect of genetic variants involved in atorvastatin transport/metabolism and correlate their lipid-lowering efficacy. Materials & methods: Genotyping was performed using 5?-hydrolysis probe method (n = 412), and the study evaluated the treatment response in 86 patients. Results: Significant reduction in total cholesterol and low-density lipoprotein cholesterol (LDL-C) were observed in SLCO1B1-rs4149056, rs4363657 and ABCB1-rs1045642 genotypes. The combined genotypes of ABCB1 and SLCO1B1 showed a strong synergistic effect in reducing the total cholesterol and LDL-C. Diabetes and smoking were observed to influence the LDL-C reduction. Conclusion: The genetic variants of SLCO1B1 and ABCB1 predict the lipid-lowering efficacy of atorvastatin, and this may be useful in genotype-guided statin therapy for coronary artery disease patients.引言：阿托伐他汀（Atorvastatin）的治疗应答存在显著的个体间差异，进而限制了该药物在冠状动脉疾病（coronary artery disease）患者中的临床疗效。 研究目的：本研究旨在探究参与阿托伐他汀转运/代谢过程的遗传变异的作用，并分析其与该药物调脂疗效的相关性。 材料与方法：采用5'-水解探针法完成基因分型（总样本量n=412），并对其中86例患者的治疗应答情况进行评估。 结果：在SLCO1B1-rs4149056、rs4363657及ABCB1-rs1045642基因型携带者中，总胆固醇与低密度脂蛋白胆固醇（LDL-C）水平均出现显著下降。ABCB1与SLCO1B1的联合基因型在降低总胆固醇及LDL-C水平方面展现出显著的协同效应。糖尿病与吸烟可对LDL-C的降低效果产生影响。 结论：SLCO1B1与ABCB1的遗传变异可预测阿托伐他汀的调脂疗效，该发现可为冠状动脉疾病患者的基因型指导下的他汀类药物治疗提供参考依据。