Department of Clinical Pharmacy, University of Michigan College of Pharmacy.
Division of Cardiovascular Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan.
Pharmacogenet Genomics. 2020 Dec;30(9):208-211. doi: 10.1097/FPC.0000000000000412.
The most common adverse drug reaction from statins are statin-associated muscle symptoms (SAMS), characterized by myopathy (weakness), myalgia (muscle pain), and commonly elevation in serum creatine kinase. All statins are substrates of the organic anion transporter 1B1 (OATP1B1; gene: SLCO1B1), albeit to different degrees. A genetic polymorphism in SLCO1B1, c.521T>C (rs4149056), markedly decreases OATP1B1 function. The literature is currently unclear as to whether SLCO1B1 c.521T>C is significantly associated with discontinuation of atorvastatin specifically due to SAMS. Our hypothesis was that individuals carrying the SLCO1B1 decreased function 521C allele are more likely to discontinue atorvastatin due to SAMS. This was a retrospective analysis of survey data from 379 Caucasians genotyped for rs4149056 and treated with atorvastatin for at least 12 months. Crude and multivariable logistic regression, adjusted for established risk factors for SAMS, determined the association of SLCO1B1 c.521T>C with discontinuation of atorvastatin due to SAMS (SLCO1B1 521T-homozygotes vs. 521C-carriers). The sample was 51% male, with a mean age of 57 years (SD = 11). Sixty-one percent of participants reported discontinuing atorvastatin due to SAMS, and 32% overall carried the 521C allele. SLCO1B1 521C-carrier status was not a significant predictor of atorvastatin discontinuation in any model: crude OR = 1.07; 95% CI, 0.68-1.66; P = 0.78 and adjusted OR = 1.07; 95% CI, 0.68-1.69; P = 0.76. The results were similar in a sub-group of participants treated with higher doses of atorvastatin (>20 mg). In summary, SLCO1B1 c.521T>C was not significantly associated with discontinuation of atorvastatin therapy due to SAMS.
他汀类药物最常见的不良反应是他汀类药物相关肌肉症状（SAMS），其特征为肌病（无力）、肌痛（肌肉疼痛），常伴有血清肌酸激酶升高。所有他汀类药物都是有机阴离子转运蛋白 1B1（OATP1B1；基因：SLCO1B1）的底物，尽管程度不同。SLCO1B1 中的遗传多态性 c.521T>C（rs4149056）显著降低了 OATP1B1 的功能。目前文献尚不清楚 SLCO1B1 c.521T>C 是否与阿托伐他汀因 SAMS 而停药有显著相关性。我们的假设是，携带 SLCO1B1 功能降低的 521C 等位基因的个体更有可能因 SAMS 而停用阿托伐他汀。这是对 379 名高加索人进行 rs4149056 基因分型并接受阿托伐他汀治疗至少 12 个月的调查数据进行的回顾性分析。采用未经调整和调整了 SAMS 既定危险因素的多变量逻辑回归来确定 SLCO1B1 c.521T>C 与因 SAMS 停用阿托伐他汀之间的关联（SLCO1B1 521T-纯合子与 521C-携带者）。该样本中 51%为男性，平均年龄为 57 岁（标准差=11）。61%的参与者报告因 SAMS 而停用阿托伐他汀，总体而言，32%的参与者携带 521C 等位基因。在任何模型中，SLCO1B1 521C 携带状态均不是阿托伐他汀停药的显著预测因素：未经调整的 OR=1.07；95%CI，0.68-1.66；P=0.78，调整后的 OR=1.07；95%CI，0.68-1.69；P=0.76。在接受较高剂量阿托伐他汀（>20mg）治疗的亚组参与者中，结果相似。总之，SLCO1B1 c.521T>C 与因 SAMS 而停用阿托伐他汀治疗无显著相关性。
