SLCO1B1

SLCO1B1, or solute carrier organic anion transporter family member 1B1, is a human gene encoding the hepatic transporter protein OATP1B1 (organic anion transporting polypeptide 1B1). It is part of the SLCO/SLC01 family. The protein comprises 12 transmembrane domains and is localized on the basolateral (blood-facing) membrane of hepatocytes, where it mediates the sodium-independent uptake of a broad range of endogenous and exogenous organic anions, including bile acids, bilirubin conjugates, hormones, and various drugs. Expression is highest in the liver with lower levels in kidney and intestine.

Genetic variation: Many SLCO1B1 alleles exist; the most studied is SLCO1B1*5 (rs4149056; c.521T>C; p.V174A), which reduces transport activity. Other haplotypes, including *1 (wild-type), *1a, *1b, *15, and *17, show varying function. Variation influences hepatic uptake and systemic exposure of substrates, particularly statins.

Clinical significance: Reduced-function variants are associated with higher plasma concentrations of statins and an increased risk of statin-induced myopathy, especially with simvastatin or at higher doses. CPIC and other pharmacogenomics guidelines note the potential for genotype-guided dosing. Inhibitors of OATP1B1 and drug-drug interactions can further affect disposition of substrates such as statins, methotrexate, and bosentan.

The gene is a major determinant of hepatic drug disposition and pharmacokinetics and is frequently considered in pharmacogenomic testing to guide therapy, particularly with statins.