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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients treated with statin. | Patients with hypercholesterolemia treated with rosuvastatin 10 mg daily or simvastatin 40 mg daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rosuvastatin 10mg | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Genome-wide analysis of DNA sample | Presence or absence of single-nucleotide polymorphisms (SNPs) at over 700,000 points on the DNA samples will be analyzed using a whole-genome scan with the Illumina Omini Express BeadChip to identify which of these SNPs are associated with the LDL cholesterol reduction with rosuvastatin. | DNA samples taken after 4 weeks on statin treatment. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with hypercholesterolemia attending medical clinics in Hong Kong who were eligible for statin treatment according to local guidelines in Hong Kong and willing to give informed consent for DNA analysis.
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| Name | Affiliation | Role |
|---|---|---|
| BRIAN TOMLINSON, MD | Chinese University of Hong Kong | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brian Tomlinson | Hong Kong | Hong Kong |
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| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
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| D009750 |
| Nutritional and Metabolic Diseases |
| D006845 |
| Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |