POPULATION SOURCED DISCOVERY OF GENETIC VARIANTS IN STATIN METABOLISM

Abstract

3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are one of the most prescribed drugs for the prevention of cardiovascular disease and act by reducing plasma low-density lipoprotein (LDL) cholesterol. In Singapore, 47% of adult patients use either atorvastatin or simvastatin. Statin medications are known for their various lipid independent effects and these effects can contribute to clinical decision making regarding the prescription of statins. As a whole, this thesis demonstrates the robustness of the two-time point blood draw protocol as a novel method to evaluate drug pharmacokinetics through time normalisation. The knowledge presented also provides a foundation for future clinical studies and clinical trials that look to explore variability in drug concentrations and their ratios in patient populations to evaluate potential differences in drug metabolism as well as the use of drug and drug metabolite concentrations as potential outcomes in future pharmacogenomic studies.