Pharmacogenetics of response to statins.
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) are among the most commonly prescribed drugs worldwide. On average, statins improve lipid profiles and have been shown to have ancillary beneficial effects on inflammation, platelet activity, and endothelial function. However, variability in drug response exists regardless of the measured phenotype, and genetic variability may be a contributing factor. Recently, there has been an interesting shift in statin pharmacogenetic studies. Novel study designs have been employed and nontraditional candidate genes have been investigated in relation to both lipid and nonlipid responses to statins. This review outlines earlier pharmacogenetic studies and highlights newly published findings that expand on previous work. Furthermore, a framework is provided in which the necessary next steps in research are described, with the ultimate goal of translating pharmacogenetic findings into clinically meaningful changes in patient care.
Zineh
Issam
I
University of Florida College of Pharmacy, Department of Pharmacy Practice and Center for Pharmacogenomics, Gainesville, FL 32610, USA. zineh@cop.ufl.edu
D001057:Apolipoproteins E / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D003327:Coronary Disease / Q000188:drug therapy* / Q000235:genetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D019924:Embryo Disposition; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics
D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A