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Pharmacogenomics. 2016 Aug;17(13):1405-14. doi: 10.2217/pgs-2016-0071. Epub 2016 Jun 14.

Rare variants in known and novel candidate genes predisposing to statin-associated myopathy.

Author information

1
Laboratory of Experimental Hepatology, Center for Experimental Medicine, Institute for Clinical & Experimental Medicine, Prague, Czech Republic.
2
Institute of Inherited Metabolic Diseases, First Medical Faculty, Charles University, Prague, Czech Republic.
3
Laboratory for Atherosclerosis Research, Center for Experimental Medicine, Institute for Clinical & Experimental Medicine, Prague, Czech Republic.
4
Third Medical Department, First Faculty of Medicine, Charles University & General Faculty Hospital, Prague, Czech Republic.
5
Preventive Cardiology Department, Institute for Clinical & Experimental Medicine, Prague, Czech Republic.

Abstract

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.

KEYWORDS:

CLCN1; atorvastatin; gene; myopathy; rosuvastatin; simvastatin; statin

PMID:
27296017
DOI:
10.2217/pgs-2016-0071
[Indexed for MEDLINE]

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