Seventeen years of statin pharmacogenetics: a systematic review

Pharmacogenomics. 2016;17(2):163-80. doi: 10.2217/pgs.15.158. Epub 2015 Dec 15.

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.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • Adaptor Proteins, Vesicular Transport / genetics
  • Apolipoproteins E / genetics
  • Cardiovascular Diseases / prevention & control
  • Cholesterol, LDL / blood
  • Genetic Loci
  • Genome-Wide Association Study
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Lipid Metabolism / genetics
  • Lipoprotein(a) / genetics
  • Liver-Specific Organic Anion Transporter 1
  • Neoplasm Proteins / genetics
  • Organic Anion Transporters / genetics
  • Polymorphism, Single Nucleotide

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Adaptor Proteins, Vesicular Transport
  • Apolipoproteins E
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoprotein(a)
  • Liver-Specific Organic Anion Transporter 1
  • Neoplasm Proteins
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • sortilin