Genome Wide Association and Pharamcokinetics of Statin Therapies
We study genetic predictors of statin metabolism, efficacy, and tolerability in a post-cardiac event population.
Large numbers of people currently take statins to manage cholesterol levels and many more will do so in the future. However, efficacy (the reduction in total and low density lipoprotein and increase in high density lipoprotein) and side effects (muscle pain and damage, liver damage, and others) are highly variable within the population. Statin therapy is especially important for patients who have already had cardiac events. In this clinical study, we examine patients' genomic influences on statin (atorvastatin and simvastatin) metabolism, efficacy and tolerability by combining a genome-wide association study (GWAS) of approximately a half-million single nucleotide polymorphisms (SNPs) with population pharmacokinetics to find the contribution of genomic variants to differential statin metabolism. This is then further related to clinical outcomes of interest, such as dosage required for cholesterol level management and drug tolerability. We also examine the feasibility of probing into particular mechanisms of drug metabolism and trafficking thru the body via these genetic variants.In collaboration with Prof. Chester Drum at National University Hospital, Singapore