Pharmacogenomics of statin response

Although statin therapy has been shown to reduce substantially the risk for cardiovascular disease in multiple patient subgroups, there is wide inter-individual variation in statin efficacy, in terms of both plasma lipoprotein response and clinical outcome.

A number of studies have reported that polymorphisms in genes affecting statin pharmacodynamics and pharmacokinetics are associated with measures of statin efficacy, but the magnitude of variation in statin response that could be explained by these associations is small. Genome-wide association studies may yield a more comprehensive set of markers for predicting statin efficacy and muscle toxicity. For the results of these analyses to have clinical value, however, there remains a need to replicate findings in multiple populations, to connect effects on LDL and other biomarkers with clinical outcomes, and to determine whether the associations apply to each individual statin.

Satisfying these requirements for clinical applicability will be challenging, but discovery of specific genotypes that influence statin efficacy and characterization of their functional effects in cellular or animal model systems may enhance our understanding of determinants of cardiovascular disease risk. They may also allow us to identify pathways that may be targeted to yield effective prevention and treatment.