已知及新发现的与他汀类药物相关性肌病相关的候选基因中的罕见变异。
Rare variants in known and novel candidate genes predisposing to statin-associated myopathy.
作者信息
Neřoldová Magdaléna, Stránecký Viktor, Hodaňová Kateřina, Hartmannová Hana, Piherová Lenka, Přistoupilová Anna, Mrázová Lenka, Vrablík Michal, Adámková Věra, Hubáček Jaroslav A, Jirsa Milan, Kmoch Stanislav
机构信息
Laboratory of Experimental Hepatology, Center for Experimental Medicine, Institute for Clinical & Experimental Medicine, Prague, Czech Republic.
Institute of Inherited Metabolic Diseases, First Medical Faculty, Charles University, Prague, Czech Republic.
出版信息
Pharmacogenomics. 2016 Aug;17(13):1405-14. doi: 10.2217/pgs-2016-0071. Epub 2016 Jun 14.
AIM
Genetic variants affecting statin uptake, metabolism or predisposing to muscular diseases may confer susceptibility to statin-induced myopathy. Besides the SLCO1B1 rs4149056 genotype, common genetic variants do not seem to determine statin-associated myopathy. Here we aimed to address the potential role of rare variants.
METHODS
We performed whole exome sequencing in 88 individuals suffering from statin-associated myopathy and assessed the burden of rare variants using candidate-gene and exome-wide association analysis.
RESULTS
In the novel candidate gene CLCN1, we identified a heterozygote truncating mutation p.R894* in four patients. In addition, we detected predictably pathogenic case-specific variants in MYOT, CYP3A5, SH3TC2, FBXO32 and RBM20.
CONCLUSION
These findings support the role of rare variants and nominate loci for follow-up studies.
目的
影响他汀类药物摄取、代谢或易患肌肉疾病的基因变异可能会使人易患他汀类药物诱发的肌病。除了SLCO1B1 rs4149056基因型外，常见的基因变异似乎并不能决定他汀类药物相关的肌病。在此，我们旨在探讨罕见变异的潜在作用。
方法
我们对88例患有他汀类药物相关肌病的个体进行了全外显子组测序，并使用候选基因和全外显子组关联分析评估了罕见变异的负担。
结果
在新的候选基因CLCN1中，我们在4例患者中鉴定出一个杂合性截短突变p.R894*。此外，我们在MYOT、CYP3A5、SH3TC2、FBXO32和RBM20中检测到可预测的致病性病例特异性变异。
结论
这些发现支持了罕见变异的作用，并为后续研究确定了基因座。
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