Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP, Brazil CEP 05403-000.
Eur J Clin Pharmacol. 2012 Mar;68(3):273-9. doi: 10.1007/s00228-011-1125-1. Epub 2011 Sep 18.
Recent studies reported the association of SLCO1B1 haplotypes with the development of musculoskeletal side effects during simvastatin use. The aim was to evaluate the pharmacogenetic association of SLCO1B1 haplotypes with atorvastatin-induced myalgia in a sample of individuals on high-dose atorvastatin regimens.
One hundred and forty-three patients with familial hypercholesterolemia were followed for at least 12 months while receiving atorvastatin. Genotypes for the rs2306283 (c.A388G) and rs4149056 (c.T521C) polymorphisms were detected by high-resolution melting analysis. These markers form four distinct haplotypes (*1A, *1B, *5 and *15).
During the follow-up period, 14 (9.8%) patients developed myalgia and 16 (11.2%) presented CK levels more than 3 times the upper limit of the normal range. No association of the SLCO1B1 rs2306283 and rs4149056 genotypes or haplotypes with the presence of myalgia or creatine kinase (CK) values was found. Presence of rs2306283 AG + GG genotypes was not associated with increased risks of myalgia or abnormal CK values (OR 2.08, 95% CI 0.62-7.00, p = 0.24 and OR 0.51, 95% CI 0.21-1.26, p = 0.15 respectively). The presence of rs4149056 TC + CC genotypes was also not associated with increased risk of myalgia or abnormal CK values (OR 2.24, 95% CI 0.47-10.72, p = 0.31 and OR 1.51, 95% CI 0.57-3.96, p = 0.41 respectively).
Our findings reaffirm that the SLCO1B1 genetic risk appears to be greater in those patients receiving simvastatin compared with those receiving atorvastatin. This suggests that the importance of SLCO1B1 haplotypes depends on the specific statin that has been used.
最近的研究报告称 SLCO1B1 单倍型与辛伐他汀使用过程中肌肉骨骼副作用的发展有关。本研究旨在评估 SLCO1B1 单倍型与阿托伐他汀诱导的肌痛在接受高剂量阿托伐他汀治疗方案的个体中的遗传关联。
143 名家族性高胆固醇血症患者在接受阿托伐他汀治疗至少 12 个月时接受随访。采用高分辨率熔解分析检测 rs2306283（c.A388G）和 rs4149056（c.T521C）多态性的基因型。这两个标记形成四个不同的单倍型（*1A、*1B、5 和15）。
在随访期间，14 名（9.8%）患者出现肌痛，16 名（11.2%）患者肌酸激酶（CK）水平超过正常上限的 3 倍。未发现 SLCO1B1 rs2306283 和 rs4149056 基因型或单倍型与肌痛或肌酸激酶（CK）值的存在有关。rs2306283 AG+GG 基因型的存在与肌痛或异常 CK 值的风险增加无关（OR 2.08，95%CI 0.62-7.00，p=0.24 和 OR 0.51，95%CI 0.21-1.26，p=0.15）。rs4149056 TC+CC 基因型的存在也与肌痛或异常 CK 值的风险增加无关（OR 2.24，95%CI 0.47-10.72，p=0.31 和 OR 1.51，95%CI 0.57-3.96，p=0.41）。
我们的研究结果再次证实，与接受阿托伐他汀治疗的患者相比，接受辛伐他汀治疗的患者 SLCO1B1 遗传风险似乎更大。这表明 SLCO1B1 单倍型的重要性取决于所使用的特定他汀类药物。
