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Drug Res (Stuttg) 2019; 69(04): 185-193
DOI: 10.1055/a-0677-2944
Review
© Georg Thieme Verlag KG Stuttgart · New York

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

Xingang Li
1   Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
2   Monogenic Disease Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China
,
Shusen Sun
3   College of Pharmacy and Health Sciences, Western New England University, Springfield, Massachusetts, United States of America
,
Xiaowei Xu
4   Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
,
Zhigang Zhao
1   Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
,
Wei Li
2   Monogenic Disease Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China
› Author Affiliations
Further Information

Publication History

received 08 June 2018

accepted 06 August 2018

Publication Date:
07 September 2018 (online)

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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
 

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