Rare variants in known and novel candidate genes predisposing to statin-associated myopathy
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
PubMed
27296017
DOI
10.2217/pgs-2016-0071
Knihovny.cz E-resources
- Keywords
- CLCN1, atorvastatin, gene, myopathy, rosuvastatin, simvastatin, statin,
- MeSH
- Genome-Wide Association Study MeSH
- Chloride Channels genetics MeSH
- Adult MeSH
- Exome genetics MeSH
- Genetic Variation MeSH
- Genotype MeSH
- Middle Aged MeSH
- Humans MeSH
- Muscular Diseases chemically induced epidemiology genetics MeSH
- Liver-Specific Organic Anion Transporter 1 genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects MeSH
- Rare Diseases genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Chloride Channels MeSH
- CLC-1 channel MeSH Browser
- Liver-Specific Organic Anion Transporter 1 MeSH
- SLCO1B1 protein, human MeSH Browser
- Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH
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.
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