Genetic Determinants of Statin-induced Myopathy: A Network Meta-analysis of Observational Studies
Abstract
Introduction: Statin-induced myopathy (SIM) is a prevalent adverse event impacting treatment adherence. Despite extensive exploration of single nucleotide polymorphisms (SNPs), conflicting evidence obscures their role in SIM incidence, prompting this network meta-analysis.
Methods: Observational studies meeting eligibility criteria (patients on any statin with reported SNPs and SIM details) were systematically reviewed. Severe SIM was defined as creatine kinase elevations exceeding 10 times the upper limit of normal. Mixed treatment comparison pooled estimates were generated from direct and indirect pooled estimates, represented by odds ratios (OR) with 95% confidence intervals (CI), and validated via bootstrap analysis.
Results: Thirty-four studies (26,152 participants) examining genotypes spanning drug transporters, metabolizing enzymes, reactive oxygen species production, and myopathy-related genes were analyzed. Significant associations were observed with drug transporters (OR: 1.4; 95% CI: 1.04, 1.5). Notably, solute carrier organic anion transporter 1B1 (SLCO1B1) (rs4149056) exhibited a moderate association with SIM (OR: 2.1; 95% CI: 1.7, 2.6), validated by bootstrap analysis (OR: 2.1; 95% CI: 1.7, 2.8). Similar associations were found for severe SIM with SLCO1B1 (rs4149056) (OR: 3.8; 95% CI: 1.4, 10.4) and ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs2373588) (OR: 2.8; 95% CI: 1.4, 5.4). Intraclass differences in genetic predictor risks were noted among…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 26,152 participants or records.
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