title: Pharmacogenetics of statins: achievements, whole-genome analyses and future perspectives.
abstract: Statins are the most commonly prescribed class of drug worldwide and therapy is highly effective in reducing low-density lipoprotein cholesterol levels and cardiovascular events. However, there is large variability in clinical response to statin treatment. Recent research provides evidence that genetic variation contributes to this variable response to statin treatment. Until recently, pharmacogenetic studies have used mainly candidate gene approaches to investigate these effects. Since candidate gene studies explain only a small part of the observed variation and results have often been inconsistent, genome-wide association (GWA) studies may be a better approach. In this paper the most important candidate gene studies and the first published GWA studies assessing statin response are discussed. Moreover, we describe the PHASE study, an EU-funded GWA study that will investigate the genetic variation responsible for the variation in response to pravastatin in a large randomized clinical trial.
authors.affiliation: Department of Gerontology & Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Postmus
authors.forename: Jeffrey J W
authors.initials: JJ
authors.lastname: Verschuren
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
mesh_terms: D054316:Biomarkers, Pharmacological; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood; D010597:Pharmacogenetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D054316:Biomarkers, Pharmacological; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL