Correlation between single-nucleotide polymorphisms and statin-induced myopathy: a mixed-effects model meta-analysis.

Area of Science:

• Pharmacogenomics
• Genetic Epidemiology
• Clinical Pharmacology

Background:

• Statin-induced myopathy (SIM) is a common adverse effect of statin therapy.
• Genetic factors, particularly single-nucleotide polymorphisms (SNPs), are increasingly recognized as influencing SIM risk.
• Understanding these genetic correlations can personalize statin treatment and mitigate adverse events.

Purpose of the Study:

• To conduct a meta-analysis evaluating the association between specific SNPs and the risk of developing SIM.
• To identify genetic markers that predict susceptibility or resistance to statin-induced muscle damage.

Main Methods:

• A comprehensive literature search was performed across PubMed, Embase, and Cochrane Library databases for studies on SIM up to April 2019.
• Data from 32 studies, encompassing 21,692 individuals and nine statins, were analyzed for 10 SNPs across five genes.
• Statistical models (heterozygous, homozygous, dominant, recessive) were employed to assess SNP-gene-SIM risk correlations.

Main Results:

• The SLCO1B1 rs4149056 SNP was significantly associated with an increased risk of SIM across multiple genetic models (p ≤ 0.017).
• Conversely, the SLCO1B1 rs4363657 SNP showed a reduced risk of SIM in heterozygous and dominant models (p ≤ 0.048).
• Specific allele carriers exhibited differential SIM risk: rs4149056 C allele with simvastatin and rs9806699 A allele with rosuvastatin.

Conclusions:

• The meta-analysis confirms a significant correlation between SLCO1B1 SNPs (rs4149056, rs4363657) and GATM SNP (rs9806699) with the risk of statin-induced myopathy.
• These findings highlight the role of specific genetic variations in predicting SIM risk.
• The identified SNPs may serve as valuable biomarkers for personalized statin therapy selection and risk stratification.