The pharmacogenomics of statins

The statin class of cholesterol-lowering drugs have been used for decades to successfully lower plasma cholesterol concentrations and cardiovascular risk. Adverse effects of statins are generally considered mild, but increase with age of patients and polypharmacy. One aspect of statin therapy that is still difficult for prescribers to predict is the individual's response to statin therapy. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect statin efficacy and safety. In this review, a number of candidates that affect statin pharmacokinetics and pharmacodynamics are discussed. Some of these candidates, in particular those involved in import and efflux of statins, have now been linked to increased risk of side effects. Furthermore, pharmacogenomic studies continue to reveal new players that are involved in the fine-tuning of the complex regulation of cholesterol homeostasis and response to statins.

Major candidate genes implicated in causing variation in efficacy and safety of statin therapy. The majority of these genes are expressed in hepatocytes. The bile canaliculus is indicated in green, while statin molecules are indicated in red. ABCG2 and ABCB1 in addition play a role in excretion of statins in enterocytes.Figure optionsDownload high-quality image (76 K)Download as PowerPoint slide