Transporter pharmacogenetics and statin toxicity.
Polymorphisms in transporter genes can have profound effects on statin pharmacokinetics. In particular, a common genetic variant of organic anion-transporting polypeptide 1B1 reduces the hepatic uptake of many statins, increasing the risk of statin-induced myopathy. Similarly, genetically impaired adenosine triphosphate (ATP)-binding cassette G2 transporter efflux activity results in a marked increase in systemic exposure to various statins. Importantly, the effects of these genetic polymorphisms differ depending on the specific statin that is used. This provides a rational basis for the individualization of lipid-lowering therapy.
Niemi
M
M
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. mikko.niemi@helsinki.fi
D000818:Animals; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000378:metabolism* / Q000633:toxicity; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D026901:Membrane Transport Proteins