MedGen

Statins are among the most commonly prescribed drugs in the world to treat hypercholesterolemia and prevent cardiovascular diseases. They effectively lower cholesterol levels by inhibiting the HMG-CoA reductase to reduce cholesterol synthesis. Though well tolerated in general, the most common statin side effect is statin-associated musculoskeletal symptoms (SAMS) which range from myalgia, myopathy to fatal rhabdomyolysis, especially when statins are administered at higher doses and with certain other medications. Genetic variations in genes encoding the statin transporters, SLCO1B1 and ABCG2, and metabolizing enzyme, CYP2C9, have been shown to affect systemic plasma concentrations of statins and are associated with increased risk for SAMS. Guidelines regarding the use of pharmacogenomic tests in dosing for statins have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for simvastatin, atorvastatin, lovastatin, pravastatin and pitavastatin based on SLCO1B1 phenotype; rosuvastatin based on SLCO1B1 and ABCG2 phenotypes; and fluvastatin based on SLCO1B1 and CYP2C9 phenotypes. It serves as a guide for selecting the most appropriate statin and the optimal dose if pharmacogenetic test results are available. [from PharmGKB]

Rotor syndrome is characterized by mild conjugated and unconjugated hyperbilirubinemia that usually begins shortly after birth or in childhood. Jaundice may be intermittent. Conjunctival icterus may be the only clinical manifestation. [from GeneReviews]