SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink.
SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink.
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DOI：
10.1038/clpt.2013.161
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发表时间：
2013-12
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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作者：
本研究旨在确定是否可以使用英国临床实践研究数据链识别他汀类药物诱导的肌病患者，是否可以获得DNA，以及是否可以复制先前报道的他汀类药物肌病与SLCO 1B 1 c.521T>C和COQ 2 rs 4693075多态性的相关性。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。多因素Logistic回归分析显示SLCO 1B 1 c.521 T>C单核苷酸多态性是一个显著的危险因素（P = 0.009），所有肌病的每个变异等位基因的比值比（OR）为2.06（1.32-3.15），严重肌病（CPK > 10× ULN，和/或横纹肌溶解; n = 23）为4.09（2.06-8.16）。COQ 2 rs 4693075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功效有限。我们的数据复制了SLCO 1B 1变异体与他汀类药物诱导的肌病的关联。此外，我们还展示了电子病历如何提供一种时间和成本效益的方法来招募药物遗传学研究中出现严重药物不良反应的患者。
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.
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影响因子：
6.7
作者：
Niemi, M.
通讯作者：
Niemi, M.
影响因子：
24
作者：
Marcoff, Leo;Thompson, Paul D.
通讯作者：
Thompson, Paul D.
影响因子：
3.4
作者：
Ford, GA;Wood, SM;Daly, AK
通讯作者：
Daly, AK
DOI：
10.4161/derm.2.2.13509
发表时间：
2010-01-01
期刊：
DERMATO-ENDOCRINOLOGY
影响因子：
--
作者：
Linde, Randy;Peng, Lihong;Feldman, David
通讯作者：
Feldman, David
影响因子：
6.7
作者：
Wilke, R. A.;Ramsey, L. B.;Niemi, M.
通讯作者：
Niemi, M.