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Genetic and Clinical Factors Are Associated With Statin-Related Myotoxicity of Moderate Severity: A Case–Control Study

Lookup NU author(s): Sal Bakar, Dr Peter Avery, Dr Colin Brown, Professor Ann Daly, Professor Farhad Kamali

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley , 2018.

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Abstract

© 2017, The American Society for Clinical Pharmacology and Therapeutics. We evaluated the contribution of patient-specific clinical and genetic factors to statin-related muscle toxicity (SRM) without a significant creatine kinase elevation (125 cases related to simvastatin or atorvastatin and 481 controls). The association between 12 single nucleotide polymorphisms (SNPs) in nine candidate genes and clinical factors with SRM was evaluated. Of the 12 SNPs genotyped, only rs4149056 in SLCO1B1 was associated with SRM in univariate analysis (with any statin, odd ratio (OR)=1.73, 95% confidence interval (CI)=1.14-2.62, P=0.010) and this association was influenced by sex (P=0.006) and BMI (P=0.02). In multivariate and binary logistic regression analyses, SLCO1B1 rs4149056 genotype (OR=1.66, 95% CI: 1.08-2.54, P=0.014) and sex (OR=1.72, 95% CI=1.15-2.59, P=0.006) were independently associated with muscle toxicity related to statin treatment. Patient-specific genetic and clinical factors associated with increased systemic exposure to statins are implicated in the full spectrum of SRM, including myalgia in addition to severe myopathy.


Publication metadata

Author(s): Bakar NS, Neely D, Avery P, Brown C, Daly AK, Kamali F

Publication type: Article

Publication status: Published

Journal: Clinical Pharmacology and Therapeutics

Year: 2018

Volume: 104

Issue: 1

Pages: 178-187

Print publication date: 01/07/2018

Online publication date: 22/09/2017

Acceptance date: 19/09/2017

Date deposited: 22/12/2017

ISSN (print): 0009-9236

ISSN (electronic): 1532-6535

Publisher: Wiley

URL: https://doi.org/10.1002/cpt.887

DOI: 10.1002/cpt.887


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