并且变体协同影响了南印度冠状动脉疾病患者对阿托伐他汀的治疗反应。

and variants synergistically influence the atorvastatin treatment response in South Indian coronary artery disease patients.

机构信息

Department of Genetics, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.

Center for Vascular and Inflammatory Disease, University of Maryland Baltimore, School of Medicine, Baltimore, MD 21201, USA.

出版信息

Pharmacogenomics. 2022 Aug;23(12):683-694. doi: 10.2217/pgs-2022-0044. Epub 2022 Aug 15.

DOI:10.2217/pgs-2022-0044

PMID:35968761

Abstract

Atorvastatin exhibits wide interindividual variability in treatment response, limiting the drug efficacy in coronary artery disease patients. To study the effect of genetic variants involved in atorvastatin transport/metabolism and correlate their lipid-lowering efficacy. Genotyping was performed using 5'-hydrolysis probe method (n = 412), and the study evaluated the treatment response in 86 patients. Significant reduction in total cholesterol and low-density lipoprotein cholesterol (LDL-C) were observed in -rs4149056, rs4363657 and -rs1045642 genotypes. The combined genotypes of and showed a strong synergistic effect in reducing the total cholesterol and LDL-C. Diabetes and smoking were observed to influence the LDL-C reduction. The genetic variants of and predict the lipid-lowering efficacy of atorvastatin, and this may be useful in genotype-guided statin therapy for coronary artery disease patients.

摘要

阿托伐他汀在治疗反应方面表现出广泛的个体间变异性，限制了其在冠心病患者中的疗效。本研究旨在探讨参与阿托伐他汀转运/代谢的遗传变异体的作用，并对其降脂疗效进行相关性分析。采用 5′-水解探针法进行基因分型（n=412），并对 86 例患者进行治疗反应评估。结果显示，-rs4149056、rs4363657 和 -rs1045642 基因型患者的总胆固醇和低密度脂蛋白胆固醇（LDL-C）显著降低。和联合基因型在降低总胆固醇和 LDL-C 方面表现出强烈的协同作用。研究还发现，糖尿病和吸烟会影响 LDL-C 的降低。和的遗传变异体可预测阿托伐他汀的降脂疗效，这可能有助于指导冠心病患者进行基于基因型的他汀类药物治疗。