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Clin Pharmacol Ther. 2019 Jun 20. doi: 10.1002/cpt.1557. [Epub ahead of print]

Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.

Author information

1
Wolfson Centre for Personalised Medicine, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
2
Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
3
Rheumatology Department, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK.
4
NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
5
Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, USA.
6
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
7
Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
8
School of Population Health and Environmental Sciences, King's College London, London, UK.
9
Medical and Clinical Pharmacology, CHU Toulouse, Toulouse, France.
10
University Hospital, Verona, Italy.
11
Health e-Research Centre, School of Health Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK.
12
Faculty of Science, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.

Abstract

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 × 10-5 ) 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.

PMID:
31220337
DOI:
10.1002/cpt.1557

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