Genetics, statins, and lipid metabolism in cardiovascular disease

Postmus, I. (2015)

Doctoral Thesis

Aim of this thesis was to investigate pharmacogenetic effects on response to statin treatment and the genetics of lipid metabolism and cardiovascular disease. In chapter 4 the first results of the Genomic investigation of Statin Therapy (GIST) consortium are presented. We identified and validated two new GWAS loci to be associated with LDL-cholesterol response after statin treatment. In addition, we confirmed two previous identified loci. In chapter 5 we showed that we were not able to identify any loci associated with differential event reduction after statin therapy within the PROSPER study. The results presented in chapter 8 show that even at old age a genetic predisposition to high LDL-cholesterol is a risk factor for mortality. The results of this thesis show that currently the possibilities to personalize statin treatment based on genetic variants is limited. New research methods will hopefully give new opportunities to improve cardiovascular disease treatment and give more insight into the biological mechanisms of statin treatment.

• Cardiovascular disease
• Aging
• Lipid metabolism
• GWAS
• Pharmacogenetics
• Statins
• Genetics

• All authors: Postmus, I.
• Supervisor: Jukema, J.W.; Westendorp, R.G.J.
• Co-supervisor: Trompet, S.; Craen, A.J.M. de
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2015-01-28
• ISBN (print): 9789053359891