Role of Pharmacogenetics on Response to Statins: A Genotype-based Approach to Statin Therapy Outcome

Abstract

Statins are widely prescribed and very effective drugs in prevention of cardiovascular disease. There is large variability between individuals in drug response to statins. It is demonstrated that genetic variation influences the inter-individual differences in both pharmacokinetic and pharmacodynamic pathways, which leads to altered efficacy and enhanced adverse drug reactions. Pharmacogenetics aims to provide maximum clinical efficacy together with minimized adverse drug reactions and possibly letting “personalized medication” possible. Several pharmacogenetic gene studies including single nucleotide polymorphisms have been performed related to candidate genes that may impact the enzymes, metabolisms, transport systems and hence may alter pharmacokinetic and pharmacodynamic properties of statins. This article reviews, the polymorphic genes CYP3A4, CYP3A5, CYP2D6 and CYP2C9 that are members of the cytochrome P450 (CYP) enzymatic pathways in respect to their effect on altering of statin metabolism. In addition, the effects of HMG-CoA reductase and apolipoprotein E genes and their variants on lipid lowering efficacy of statins are evaluated. Variants of the other genes associated with the clinical events after statin therapy including SLCO1B1, CETP, ABCB1, ABCB2 (BRCP), KIF6 and other genes are also discussed. Since genetic markers are predictive of response to statin therapy, research in the field of pharmacogenetics aims to guide personalized treatment of hypercholesterolemia. With this purpose their potential application in clinical practice should be investigated in large cohorts of patients and especially genome-wide association studies. Further trials will determine whether any pharmacogenetic testing would be beneficial in providing a “tailoring treatment” of statins in the management of cardiovascular disease.