The last decade has seen an increase in the trend of
HMG-CoA reductase inhibitor (
statin) usage in the Western world, which does not come as a surprise noting that the latest American Heart Association heart and
stroke statistics indicate an alarming prevalence of 80 million Americans (one in three) with one or more forms of diagnosed
cardiovascular disease (CVD). Meta-analysis of several large-scale, randomized clinical trials has demonstrated
statins to be efficacious in significantly reducing CVD-associated mortality in both primary and
secondary prevention. Despite their proven efficacy,
statins have also gained attention with respect to
adverse drug reactions (ADRs) of muscle
myopathy, derangements in hepatic function and even ADRs classified as psychiatric in nature. The depletion of
cholesterol within the myocyte cell wall and/or the depletion of key intermediates within the
cholesterol synthesis pathway are hypothesized as possible mechanisms of
statin-associated ADRs. However, pharmacogenetic variability may also be a risk factor for ADRs and can include, for example,
enzymes, transporters, cell membrane receptors, intracellular receptors or components of
ion channels that contribute to the pharmacokinetics or pharmacodynamics of response to a particular drug. The
cytochrome P450 (CYP) enzymatic pathways that comprise the polymorphic genes,
CYP2D6,
CYP3A4 and
CYP3A5, and also a hepatic transporter, solute carrier
organic anion transporter (SLCO1B1), which is a single nucleotide polymorphism discovered to be associated with
statin-induced
myopathy through a genome-wide association study, are discussed with respect to their effect on altering the pharmacokinetic profile of
statin metabolism. Variants of the
Apolipoprotein E (
APO-E) gene, polymorphisms in the
cholesteryl ester transfer protein (CETP) gene, the
HMG-CoA reductase gene and other
proteins are discussed with respect to altering the pharmacodynamic profile of
statins. Pharmacogenetics and its application in medicine to individualize
drug therapy has been previously shown to be clinically and economically beneficial through quality-adjusted life-year assessment. Therefore, polymorphisms affecting the pharmacokinetic and pharmacodynamic profiles of
statins, which are widely used in
therapy, with their potential application in the personalized prescribing of
statin therapy, need further research. In this review, we update the recent literature with respect to genetic polymorphisms that may influence the pharmacokinetics and pharmacodynamics of
statin therapy, and consider the relevance of these findings to the efficacy of treatment, prevention of ADRs and what this may mean for patient tolerance and compliance.