Association Between Slco1b1 Gene Marker And Simvastatin-induced Myopathy: A Systematic Review And Meta-analysis

• By: LOGANATHAN, Mathumalar (Malaysia)
• Co-author(s): Dr Mathumalar Loganathan (Department of Clinical Pharmacy, Faculty of Pharmacy, Universiti Teknologi Mara, Selangor, Malaysia)
  
• Abstract:

  Background:
  Statin is used for the treatment of hyperlipidemia to prevent and treat myocardial infarction and stroke and reducing cardiovascular morbidity and mortality in certain patients. Statin use is commonly associated with muscle-related adverse effects, ranging from myalgia, to life-threatening rhabdomyolysis leads to non-adherence, discontinuation or reduction of statin dose by the patients. The variability of myotoxicity is caused not only by traditional clinical factors, such as female sex and diabetes, but also by genetic variations. Genetic associations with statin-induced myopathy also have been reported, but with the large numbers of candidate genes and single-nucleotide polymorphisms (SNPs) involved, a statistically convincing pooled analyses is still lacking. This study aimed to investigate the association between SLCO1B1 gene marker and the incidence of simvastatin-induced myopathy through a comprehensive meta-analysis.
  
  Methods:
  The electronic databases of PubMed, Scopus, Web of Sciences and SpringerLink were searched for publications from 2005 until 2022. The combination of the following keywords was used: (simvastatin or statin or hypercholesterol* drug or Hydroxymethylglutaryl-CoA Reductase Inhibitors) AND (myotoxicity or myalgia or muscle symptoms or creatinine kinase elevate* or muscle weakness) AND (SLCO1B1 or genetic polymorphism or hepatocytes protein or biomarker or rs4149056). The Downs and Black tool was used for assessing the quality of included studies. Nine studies were included and assessed. Cochrane Review Manager (RevMan) V.5.4 software was used for meta-analysis. The software was utilized to produce Forest Plot which illustrates heterogeneity and pooled results. The software also generated Funnel plot for assessing publication bias.
  
  Results:
  A total of 1368 articles were originally identified. After removing 347 duplicate articles, 1021 articles were left for abstract screening and full-text assessment. After abstract screening, 993 records were excluded following reading the title and abstract. 19 studies then were left for full-text assessment. After evaluating the full-text according to inclusion and exclusion criteria, 9 studies were eligible for further meta-analysis. Nine observational studies were included in the meta-analysis. The pooled analysis showed that statin-induced myopathy was significantly associated with the SLCO1B1 gene marker. The results did not have statistical significance since the combined results (the diamond) crossed the vertical “line of no effect”, with OR 0.67 and 95% CI 0.40 to 1.12. It means that the overall outcome rate in the cases group is much the same as in the control group. On the other hand, p-value of the chi-squared test is <0.00001, indicating significant heterogeneity. Moreover, the I² value is 89% suggesting considerable or high heterogeneity. A random effect model can be used in the meta-analysis since the heterogeneity is high. This shows that there is variability among the nine studies.
  
  Conclusion:
  Simvastatin and other statins are dose-dependent that can cause statin-induced myopathy. Other than that, variant C allele may be a high-risk factor also for statin-related myopathy. Anyway, in this meta-analysis, the overall outcome rate in the intervention group is similar as in the control group. Therefore, the results show that SLCO1B1 gene is not associated with risk of statin-related myopathy in individuals getting simvastatin treatment.