The Association between Genetic Polymorphisms and Simvastatin-Induced Myopathy: A Narrative Synthesis of Evidence

Xingang Li; Shusen Sun; Xiaowei Xu; Zhigang Zhao; Wei Li

doi:10.1055/a-0677-2944

Drug Research, Table of Contents

Drug Res (Stuttg) 2019; 69(04): 185-193
DOI: 10.1055/a-0677-2944

Review

The Association between Genetic Polymorphisms and Simvastatin-Induced Myopathy: A Narrative Synthesis of Evidence

Authors

Xingang Li

¹Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China

²Monogenic Disease Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China
Shusen Sun

³College of Pharmacy and Health Sciences, Western New England University, Springfield, Massachusetts, United States of America
Xiaowei Xu

⁴Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
Zhigang Zhao

¹Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
Wei Li

²Monogenic Disease Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China

Abstract

Background and study aim Genetic polymorphisms may play a role in muscular injury associated with simvastatin, but results were inconclusive. This study aimed to summarize evidence from the literature investigating the effects of genetic polymorphism on simvastatin-induced myopathy.

Methods Studies regarding the association between genetic polymorphisms and simvastatin-induced myopathy were retrieved through electronic databases from February 1, 1990 to March 15, 2018. Two authors independently extracted data, including PMID, author, publication year, country, race, age, population characteristics, drugs, definition of case and control, gene, allele, SNP position, Hardy-Weinberg equilibrium, number of genotypes (case and control), minor allele frequency of cases and controls, association, study type and the Newcastle-Ottawa scale. Due to high heterogeneity in study design and outcome measurements among the included articles, a narrative synthesis of the evidence was conducted.

Results A total of 10 association studies were identified in this study, including SLCO1B1, ABCB1, GATM, HTR3B, HTR7, RYR2 and HLA-DRB1. The evidence linking myopathy to rs4149056 in SLCO1B1 is of high quality, and this association has been reproduced in randomized trials and clinical practice-based cohorts. As for other candidate genetic markers, the evidences are limited or controversial, and additional well-designed studies with larger sample sizes, are required to further elucidate this association.

Conclusion SLCO1B1 genotype is a useful biomarker for predicting an increased risk of simvastatin-induced myopathy.

Key words

simvastatin - genetic polymorphisms - myopathy - SLCO1B1 - evidences

Full Text

References

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