Pharmacogenetics of statins: achievements, whole-genome analyses and future perspectives

Author:

Postmus Iris12,Verschuren Jeffrey JW3,de Craen Anton JM12,Slagboom P Eline24,Westendorp Rudi GJ125,Jukema J Wouter367,Trompet Stella8

Affiliation:

1. Department of Gerontology & Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

2. Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands

3. Department of Cardiology, C-2-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands

4. Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

5. Leyden Academy of Vitality & Ageing, Leiden, The Netherlands

6. Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands

7. Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands

8. Department of Gerontology & Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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