Department of Molecular and Clinical Pharmacology, Wolfson Centre for Personalised Medicine, Liverpool, UK.
Clin Pharmacol Ther. 2013 Dec;94(6):695-701. doi: 10.1038/clpt.2013.161. Epub 2013 Aug 13.
This study aimed to determine whether patients with statin-induced myopathy could be identified using the United Kingdom Clinical Practice Research Datalink, whether DNA could be obtained, and whether previously reported associations of statin myopathy with the SLCO1B1 c.521T>C and COQ2 rs4693075 polymorphisms could be replicated. Seventy-seven statin-induced myopathy patients (serum creatine phosphokinase (CPK) > 4× upper limit of normal (ULN)) and 372 statin-tolerant controls were identified and recruited. Multiple logistic regression analysis showed the SLCO1B1 c.521T>C single-nucleotide polymorphism to be a significant risk factor (P = 0.009), with an odds ratio (OR) per variant allele of 2.06 (1.32-3.15) for all myopathy and 4.09 (2.06-8.16) for severe myopathy (CPK > 10× ULN, and/or rhabdomyolysis; n = 23). COQ2 rs4693075 was not associated with myopathy. Meta-analysis showed an association between c.521C>T and simvastatin-induced myopathy, although power for other statins was limited. Our data replicate the association of SLCO1B1 variants with statin-induced myopathy. Furthermore, we demonstrate how electronic medical records provide a time- and cost-efficient means of recruiting patients with severe adverse drug reactions for pharmacogenetic studies.
本研究旨在确定英国临床实践研究数据链（United Kingdom Clinical Practice Research Datalink）是否可以识别出他汀类药物诱导的肌病患者，是否可以获得 DNA，以及先前报道的他汀类药物诱导的肌病与 SLCO1B1 c.521T>C 和 COQ2 rs4693075 多态性的关联是否可以得到复制。确定并招募了 77 名他汀类药物诱导的肌病患者（血清肌酸磷酸激酶（CPK）> 4×正常值上限（ULN））和 372 名他汀类药物耐受对照者。多变量逻辑回归分析显示，SLCO1B1 c.521T>C 单核苷酸多态性是一个显著的危险因素（P = 0.009），每个变异等位基因的比值比（OR）为 2.06（1.32-3.15），适用于所有肌病和严重肌病（CPK > 10×ULN，和/或横纹肌溶解症；n = 23）。COQ2 rs4693075 与肌病无关。荟萃分析显示 c.521C>T 与辛伐他汀诱导的肌病之间存在关联，尽管其他他汀类药物的效力有限。我们的数据复制了 SLCO1B1 变体与他汀类药物诱导的肌病之间的关联。此外，我们展示了电子病历如何为严重药物不良反应患者的药物遗传学研究提供一种省时、省钱的招募方式。
