Genome-wide Analysis of Lipid-lowering Efficacy and Drug Level of Simvastatin and Rosuvastatin

Genome-wide Analysis of Lipid-lowering Efficacy and Drug Level of the Two Commonly Used Statins, Simvastatin and Rosuvastatin.

This study will perform a genome-wide association study (GWAS) of the lipid responses to rosuvastatin and simvastatin and plasma concentrations of these two statins in a homogeneous group of Han Chinese patients.

A GWAS will be performed on about 360 Han Chinese patients with hypercholesterolaemia (which may be familial or non-familial) who have previously participated in a research project on the pharmacogenetics of statins and who have been treated with rosuvastatin and simvastatin to determine the genetic factors that may be related to the reduction in plasma low-density lipoprotein cholesterol (LDL-C) and plasma concentrations of these two statins. The lipid profiles were measured at baseline on no lipid-lowering treatment and after 4-6 week treatment of rosuvastatin 10 mg daily and after treatment with simvastatin 40 mg daily for at least 6 weeks with at least a 4-week washout period between the two treatments. Plasma concentrations of these two statins and their active metabolites about 12 hours after administration of statins have been measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Genotyping for the whole-genome scan will be carried out on the Illumina OminiExpress beadchip (Illumina, San Diego, CA). The samples will be processed using the Illumina iScan platform at the Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong (CUHK).

Inclusion Criteria:

• Clinical diagnosis of hypercholesterolemia (familial or non-familial)
• Eligible for statin treatment according to local guidelines in the Hong Kong Public Hospital system.

Exclusion Criteria:

• Taking other medication which may interact with the pharmacokinetics or lipid response to statins.
• Not willing to cooperate with study requirements.