Genome-wide association study of statin-induced myopathy in patients recruited using the UK clinical practice research datalink
| Autor: | Eunice Zhang, Joshua C. Bis, Maryse Lapeyre-Mestre, Jennifer A. Brody, Tjeerd van Staa, Bruce M. Psaty, Hector Chinoy, Ana Alfirevic, Andrea L. Jorgensen, Munir Pirmohamed, Susan R. Heckbert, Ben Francis, James S. Floyd, Anita Conforti, Mariam Molokhia, Daniel F. Carr |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Statin Databases Factual Pharmacogenomic Variants medicine.drug_class Genome-wide association study Single-nucleotide polymorphism Polymorphism Single Nucleotide Severity of Illness Index 030226 pharmacology & pharmacy Article 03 medical and health sciences 0302 clinical medicine Muscular Diseases Risk Factors Internal medicine medicine Adverse Drug Reaction Reporting Systems Humans SNP Genetic Predisposition to Disease Pharmacology (medical) adverse dug reaction genome wide association study myopathy statin Myopathy Exome Pharmacology biology Liver-Specific Organic Anion Transporter 1 business.industry Research Reproducibility of Results Articles Odds ratio United Kingdom 3. Good health Case-Control Studies 030220 oncology & carcinogenesis biology.protein Hydroxymethylglutaryl-CoA Reductase Inhibitors medicine.symptom SLCO1B1 business Genome-Wide Association Study |
| Zdroj: | Clinical Pharmacology and Therapeutics Clinical pharmacology and therapeutics Carr, D F, Francis, B, Jorgensen, A L, Zhang, E, Chinoy, H, Heckbert, S R, Bis, J C, Brody, J A, Floyd, J S, Psaty, B M, Molokhia, M, Lapeyre-Mestre, M, Conforti, A, Alfirevic, A, van Staa, T & Pirmohamed, M 2019, ' Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink ', Clinical Pharmacology & Therapeutics . https://doi.org/10.1002/cpt.1557 Carr, D F, Francis, B, Jorgensen, A L, Zhang, E, Chinoy, H, Heckbert, S R, Bis, J C, Brody, J A, Floyd, J S, Psaty, B M, Molokhia, M, Lapeyre-Mestre, M, Conforti, A, Alfirevic, A, van Staa, T & Pirmohamed, M 2019, ' Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink ', Clinical Pharmacology and Therapeutics . https://doi.org/10.1002/cpt.1557 |
| DOI: | 10.1002/cpt.1557 |
| Popis: | Statins can be associated with myopathy. We have undertaken a genomewide association study (GWAS) to discover and validate genetic risk factors for statin-induced myopathy in a “real-world” setting. One hundred thirty-five patients with statin myopathy recruited via the UK Clinical Practice Research Datalink were genotyped using the Illumina OmniExpress Exome version 1.0 Bead Chip and compared with the Wellcome Trust Case-Control Consortium (n = 2,501). Nominally statistically significant single nucleotide polymorphism (SNP) signals in the GWAS (P −5) were further evaluated in several independent cohorts (comprising 332 cases and 449 drug-tolerant controls). Only one (rs4149056/c.521C>T in the SLCO1B1 gene) SNP was genomewide significant in the severe myopathy (creatine kinase > 10 × upper limit of normal or rhabdomyolysis) group (P = 2.55 × 10−9; odds ratio 5.15; 95% confidence interval 3.13–8.45). The association with SLCO1B1 was present for several statins and replicated in the independent validation cohorts. The data highlight the role of SLCO1B1 c.521C>T SNP as a replicable genetic risk factor for statin myopathy. No other novel genetic risk factors with a similar effect size were identified. |
| Databáze: | OpenAIRE |
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