title: CETP deficiency due to a novel mutation in the CETP gene promoter and its effect on cholesterol efflux and selective uptake into hepatocytes.
abstract: OBJECTIVE
  To identify the genetic variant in the CETP gene of the proband with high HDL-C and low CETP activity and to investigate whether HDL from the CETP-deficient subject was dysfunctional in the reverse cholesterol transport (RCT) pathway.
  
  
  METHODS
  We sequenced the CETP gene and assessed its promoter activity. Cholesterol efflux and hepatic cholesteryl ester delivery studies were also performed using the proband's HDL.
  
  
  RESULTS
  A proband was a compound heterozygote for a known D459G variant and a novel 18-bp deletion mutation in the CETP promoter. This promoter mutation markedly reduced the transcriptional activity in HepG2 cells. HDL2 from this subject increased SR-BI-mediated cholesterol efflux, whereas cholesteryl ester delivery into hepatocytes was maintained.
  
  
  CONCLUSIONS
  A novel deletion mutation in the CETP promoter is associated with high HDL-C and decreased promoter activity. HDL from this CETP-deficient subject was not dysfunctional in mediating two main steps of RCT assessed in vitro.
authors.affiliation: Endocrinology and Metabolism Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Patumwan, Bangkok 10330, Thailand.
authors.forename: Wanee
authors.initials: W
authors.lastname: Plengpanich
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.forename: Suchanya
authors.initials: S
authors.lastname: Poolsuk
authors.forename: Zélie
authors.initials: Z
authors.lastname: Julia
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
authors.forename: Weerapan
authors.initials: W
authors.lastname: Khovidhunkit
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D008076:Cholesterol, HDL / Q000378:metabolism; D017353:Gene Deletion; D022781:Hepatocytes / Q000166:cytology; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D002784:Cholesterol