title: Variation at the cholesteryl ester transfer protein gene in relation to plasma high density lipoproteins cholesterol levels and carotid intima-media thickness.
abstract: BACKGROUND
  Cholesteryl ester transfer protein (CETP) plays a major role in lipoprotein metabolism. We have screened the CETP gene for mutations and polymorphisms regulating high density lipoproteins cholesterol (HDL-C) levels and the development of atherosclerosis, and found some polymorphisms (I405V and R451Q) to have minor effects.
  
  
  METHODS
  The purpose of this study was to investigate the combined effect of the several polymorphisms of the CETP gene so far found on HDL-C levels and carotid intima-media thickness (IMT), and, in addition, to study whether the recently found functional polymorphism in the promoter region of the CETP gene (C to A, - 629 relative to the first transcribed nucleotide) explains the previous associations due to linkage disequilibrium. The genotypes were determined in a population sample of 481 men and women.
  
  
  RESULTS
  There were no significant differences in plasma CETP activity or carotid IMT between the genotypes of the promoter polymorphism. The women with the CC genotype of the promoter polymorphism had the lowest HDL-C levels (P < 0.001), but no such difference was seen in men. Detected polymorphisms of the CETP gene explained about 8% of the variation in HDL-C in women and about 7 and 10% of the variation in carotid IMT in women and men, respectively. The associations of the promoter, I405V and R451Q-A373P polymorphisms with HDL-C and carotid IMT seemed to be independent of each other. The associations with IMT were independent of total HDL-C levels, suggesting that HDL subfractions may have more effect on IMT.
  
  
  CONCLUSIONS
  The CETP gene locus was found to be polymorphic and its polymorphisms explained a reasonable proportion of the variation in the degree of carotid atherosclerosis.
authors.affiliation: University of Oulu, Oulu, Finland, National Public Health Institute, Helsinki, Finland. sakari.kakko@oulu.fi
authors.forename: S
authors.initials: S
authors.lastname: Kakko
authors.forename: M
authors.initials: M
authors.lastname: Tamminen
authors.forename: M
authors.initials: M
authors.lastname: Päivänsalo
authors.forename: H
authors.initials: H
authors.lastname: Kauma
authors.forename: A O
authors.initials: AO
authors.lastname: Rantala
authors.forename: M
authors.initials: M
authors.lastname: Lilja
authors.forename: A
authors.initials: A
authors.lastname: Reunanen
authors.forename: Y A
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: M J
authors.initials: MJ
authors.lastname: Savolainen
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D014644:Genetic Variation; D006023:Glycoproteins; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D017539:Tunica Intima / Q000473:pathology*
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins