Modulation of Cholesterol 7α-Hydroxylase (CYP7A1) Activity as an Orthogonal Approach to the Management of Hypercholesterolemia
Main Applicant – A/Prof Ho Han Kiat, Department of Pharmacy, National University of Singapore

Inter-individual differences in serum lipid responses to statin treatment have been frequently reported, of which genetics is one important intrinsic contributing factor.

There is increasing evidence to show that CYP7A1, the gene responsible for driving the breakdown of cholesterol, is highly polymorphic and patients harbouring CYP7A1 polymorphisms and presenting with reduced CYP7A1 levels are associated with a reduced response to statins.

Our research has identified agents that can modulate CYP7A1 expression to trigger a change in cholesterol levels. A better understanding of the genotypic and phenotypic profile of the local population will allow us to identify the target population who can benefit from the alternative approach of bringing down cholesterol levels via controlling CYP7A1 levels in the body. As a broader aim, we seek to introduce a personalized approach to the management of hypercholesterolemia.