Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Statin Treatment [T88.7]

OMIM number: 604843 (SLCO1B1)

Dipl.-Biol. Birgit Busse

Scientific Background

One of the influencing factors on the tolerance of HMG-CoA reductase inhibitors (statins) are variants in the SLCO1B1 gene, which encodes for the organic anion transporter OATP1B1. OATP1B1 is mainly expressed on the sinusoidal membrane of human hepatocytes and is involved in the uptake of various substances from the sinusoidal blood into the liver. Besides endogenous substances, also statins are substrates of OATP1B1. Some variants in the SLOC1B1 gene have been associated with changes in the transport capacities of the OATP1B1 molecule. The C allele of the polymorphism c.521T>C leads to a decreased transport rate of the protein, which may result in a reduction in the hepatic uptake of substrates and an elevation of the plasma level of statines and other drugs.

Several studies have shown that if the C allele is present, the plasma concentration of simvastatin, pravastatin, pitavastatin, atorvastatin and rosuvastatin is significantly higher in carriers. Moreover, the risk for myopathy under high-dose therapy (e.g. 80 mg/d simvastatin) was significantly higher (OR 4.7) in these patients. For fluvastatin no elevated plasma levels were found. The frequency of the C allele is approx. 15% among the European population. Other OATP1B1 substrates are the antidiabetic repaglinide, the antihistamine fexofenadine and the active agent atrasentan.