title: Elevated cholesteryl ester transfer protein (CETP) activity, a major determinant of the atherogenic dyslipidemia, and atherosclerotic cardiovascular disease in South Asians.
abstract: OBJECTIVE
  Why South Asians are at increased risk of premature atherosclerotic cardiovascular diseases compared with other ethnic groups is not fully understood. Atherogenic dyslipoproteinemia - hypertriglyceridemia, elevated numbers of low-density lipoprotein (LDL) particles and low high-density lipoprotein cholesterol (HDL-C) - is more common in South Asians but the mechanisms responsible have not been explicated. Here we examined whether the circulating lipid transfer protein, cholesteryl ester transfer protein (CETP), plays a role in the pathogenesis of the atherogenic dyslipoproteinemia among South Asians.
  
  
  RESULTS
  CETP activity was determined by exogenous substrate assay in the serum of healthy, metabolically well-characterized individuals of South Asian and European descent (N = 244 and 238, respectively). Serum and lipoprotein lipids and apolipoproteins were measured and lipoprotein particle number and size were quantified via nuclear magnetic resonance spectroscopy. All the elements of the atherogenic dyslipoproteinemia were more severe in South Asians and CETP activity was significantly greater by 30% in South Asians compared with Europeans, adjusted for age, sex, body mass index and waist circumference (p < 0.0001). CETP activity was directly associated with serum triglycerides and inversely with HDL-C in the whole population. CETP activity was also directly related to apoB and LDL particle number. Finally, increased CETP activity was associated with pro-atherogenic reductions in HDL and LDL particle size.
  
  
  CONCLUSIONS
  We identified novel associations between elevated CETP activity and the triad of quantitative and qualitative lipoprotein abnormalities in the atherogenic dyslipidemia in South Asians, a major contributor of increased atherosclerotic cardiovascular diseases in South Asians.
authors.affiliation: Department of Pharmacology, Dalhousie University, Saint John and Halifax, Canada shirya.rashid@dal.ca shirya2004@yahoo.ca.
authors.forename: Shirya
authors.initials: S
authors.lastname: Rashid
authors.affiliation: Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Sniderman
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Melone
authors.affiliation: Department of Biostatistics, Faculty of Medicine, Toronto, University of Toronto and Cancer Care Ontario, Toronto, Canada.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Brown
authors.affiliation: LipoScience Inc., Wilmington, USA North Carolina State University, Raleigh, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Hamilton, McMaster University, Canada Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mente
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Hamilton, McMaster University, Canada Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada.
authors.forename: Karleen
authors.initials: K
authors.lastname: Schulze
authors.affiliation: Department of Pharmacology, Dalhousie University, Saint John and Halifax, Canada Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada Department of Pathology and Molecular Medicine, Hamilton, McMaster University, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McQueen
authors.affiliation: Department of Pharmacology, Dalhousie University, Saint John and Halifax, Canada Department of Clinical Epidemiology and Biostatistics, Hamilton, McMaster University, Canada Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.affiliation: Department of Pharmacology, Dalhousie University, Saint John and Halifax, Canada Department of Clinical Epidemiology and Biostatistics, Hamilton, McMaster University, Canada Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000328:Adult; D000368:Aged; D001208:Asia / Q000208:ethnology; D044466:Asian People; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology*; D015415:Biomarkers / Q000097:blood; D002170:Canada / Q000453:epidemiology; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology*; D005060:Europe / Q000208:ethnology; D005260:Female; D054624:Health Status Disparities; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D044465:White People
chemical_list: D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides
keywords: Cholesteryl ester transfer protein (CETP); HDL; LDL; South Asians; atherogenic dyslipoproteinemia; atherosclerotic cardiovascular diseases