title: Seventeen years of statin pharmacogenetics: a systematic review.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.|Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Leusink
authors.affiliation: Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.affiliation: Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D050356:Lipid Metabolism / Q000235:genetics; D017270:Lipoprotein(a) / Q000235:genetics; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000099183:Sortilin
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D033942:Adaptor Proteins, Vesicular Transport; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; D000099183:Sortilin; C116614:ABCG2 protein, human; C503999:SLCO1B1 protein, human
keywords: LDL cholesterol; candidate gene studies; genome-wide association studies; pharmacogenetics; review; statins