Seventeen years of statin pharmacogenetics: a systematic review

Abstract

Aim: We evaluated the evidence of pharmacogenetic associations with statins in a systematic review.

Methods: Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events.

Results: In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events.

Conclusion: Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice.

Keywords: LDL cholesterol; candidate gene studies; genome-wide association studies; pharmacogenetics; review; statins.