title: Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins.
abstract: Plasma high density lipoproteins (HDL) are a negative risk factor for atherosclerosis. Increased HDL is sometimes clustered in families, but a genetic basis has never been clearly documented. The plasma cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from HDL to other lipoproteins and therefore might influence HDL levels. Using monoclonal antibodies, we show that CETP is absent in two Japanese siblings who have markedly increased and enlarged HDL. Furthermore, they are homozygous for a point mutation in the 5'-splice donor site of intron 14 of the gene for CETP, a change that is incompatible with normal splicing of pre-messenger RNA. The results indicate that the family has an inherited deficiency of CETP due to a gene splicing defect, and illustrate the key role that CETP has in human HDL metabolism.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: M L
authors.initials: ML
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Inazu
authors.forename: C B
authors.initials: CB
authors.lastname: Hesler
authors.forename: L B
authors.initials: LB
authors.lastname: Agellon
authors.forename: C
authors.initials: C
authors.lastname: Mann
authors.forename: M E
authors.initials: ME
authors.lastname: Whitlock
authors.forename: Y L
authors.initials: YL
authors.lastname: Marcel
authors.forename: R W
authors.initials: RW
authors.lastname: Milne
authors.forename: J
authors.initials: J
authors.lastname: Koizumi
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005796:Genes; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000235:genetics*; D007438:Introns; D008074:Lipoproteins / Q000097:blood / Q000302:isolation & purification; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012016:Reference Values
chemical_list: D002352:Carrier Proteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; C030363:lipid transfer protein; D004247:DNA