About this condition
Statin Response (SLCO1B1)
Statin-induced myopathy, characterized by muscle pain, weakness, and in severe cases rhabdomyolysis, occurs in approximately 0.5-1% of statin users and is the most common reason for statin discontinuation. However, genetic variants in SLCO1B1 identify patients at substantially elevated risk. SLCO1B1 encodes solute carrier organic anion transporter 1B1 (OATP1B1), which actively transports statins into hepatocytes, the site of their action. The SLCO1B1*5 variant (rs4149056, c.521T>C, p.Val174Ala) increases plasma concentration of simvastatin approximately 4-17-fold depending on carrier status, substantially increasing myopathy risk.
Heterozygous carriers of SLCO1B1*5 have approximately 4.5-fold increased risk of myopathy on simvastatin; homozygous carriers face approximately 16.9-fold increased risk. This risk is specific to simvastatin and atorvastatin (to a lesser degree); rosuvastatin and pravastatin are metabolized through different pathways and pose lower myopathy risk in SLCO1B1 variant carriers. Approximately 15% of European ancestry populations carry at least one SLCO1B1*5 allele, with frequency varying significantly by ancestry. The *5 variant reduces hepatic transporter function, decreasing hepatic uptake and permitting statins to accumulate in plasma and reach systemic tissues including muscle, leading to higher myopathy risk.
SLCO1B1 genotyping enables safe, continued statin therapy for patients with prior myopathy or at elevated genetic risk. A patient identified as SLCO1B1*5 heterozygous can safely use alternative statins including rosuvastatin or pravastatin, enabling continued cardiovascular risk reduction. For patients who are SLCO1B1*5 homozygous, simvastatin is contraindicated; alternative statins with different metabolism pathways are strongly preferred. Genotype documentation in the medical record ensures that simvastatin is not prescribed inadvertently and that future providers understand the individual's statin tolerance profile.
- Gene locus
- SLCO1B1 (12p12.1), HMGCR (5q13.3)
