title: A novel homozygous mutation in CETP gene as a cause of CETP deficiency in a Caucasian kindred.
abstract: OBJECTIVE
  To analyze the cholesteryl ester transfer protein (CETP) gene and the plasma HDL phenotype in a Caucasian subject with extremely elevated plasma high density lipoprotein-cholesterol (HDL-C).
  
  
  RESULTS
  The proband, a 63-year-old male of Swedish ancestry with elevated HDL-C (208mg/dl) and apoA-I (and 272mg/dl), was found to be homozygous for a point mutation in exon 2 of CETP gene (c.109 C>T) resulting in a premature termination codon (R37X). Plasma CETP mass and activity were undetectable. Plasma HDL were characterized by predominance of large HDL with enhanced prebeta-HDL content. The proband's sons, heterozygotes for the mutation, had reduced plasma CETP activity and moderately elevated HDL-C. Serum of CETP deficient subjects showed a normal or enhanced cholesterol efflux capacity via ABCG1/SR-BI; cholesterol efflux via ABCA1 and macrophage cholesterol removal were lower than normal. The proband was healthy and had no atherosclerotic plaques in carotid or femoral arteries.
  
  
  CONCLUSIONS
  Complete CETP deficiency caused by mutations in CETP gene is exceedingly rare in Caucasians; the description of this single case indicates that CETP deficiency does not predispose to atherosclerosis in the absence of major cardiovascular risk factors.
authors.affiliation: Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Calabresi
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Elisa
authors.initials: E
authors.lastname: Pinotti
authors.forename: Monica
authors.initials: M
authors.lastname: Gomaraschi
authors.forename: Elda
authors.initials: E
authors.lastname: Favari
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Adorni
authors.forename: Franco
authors.initials: F
authors.lastname: Bernini
authors.forename: Cesare R
authors.initials: CR
authors.lastname: Sirtori
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Guido
authors.initials: G
authors.lastname: Franceschini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology; D002339:Carotid Arteries; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D008076:Cholesterol, HDL / Q000378:metabolism; D005192:Family Health; D005260:Female; D005263:Femoral Artery / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D002784:Cholesterol