title: Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects.
abstract: BACKGROUND
  The half of hyperalphalipoproteinemia (HALP) in Japan is caused by CETP gene mutations. Other than two prevalent mutations (D442G and Intron 14 splicing donor site +1G>A), some rare CETP mutations are found in Japanese HALP subjects.
  
  
  METHODS
  CETP gene analysis of genomic DNA from subjects was performed by restriction fragment length polymorphism (RFLP) and sequencing analysis. Mutations which were suspected to cause a splicing defect or a protein secretion defect were investigated in COS-1 cells transfected with a CETP minigene construct or a cDNA expression vector.
  
  
  RESULTS
  Each of three subjects was identified as a carrier of CETP gene mutation of a compound heterozygote of c.653_654delGGinsAAAC and Intron 14 splicing donor site +1G>A, a heterozygote of c.658G>A or a homozygote of L261R. The c.658G>A mutation was located at the last nucleotide of exon 7, and it was confirmed to cause splicing abnormality revealed by the CETP minigene analysis. The L261R CETP was not secreted to conditioned media of the cells.
  
  
  CONCLUSIONS
  Three novel CETP gene mutations are responsible for HALP by CETP deficiency. It is predicted that there are more rare CETP gene mutations in Japanese, and these multiple rare mutations alone or a combination with each of prevalent mutations is responsible for mild-to-moderate or marked HALP, respectively.
authors: Department of Laboratory Sciences, Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kodatsuno, Japan.
authors: Rumiko
authors: R
authors: Ohtani
authors: Akihiro
authors: A
authors: Inazu
authors: Yoshihiro
authors: Y
authors: Noji
authors: Takanobu
authors: T
authors: Wakasugi
authors: Kenji
authors: K
authors: Miwa
authors: Hayato
authors: H
authors: Tada
authors: Masa-aki
authors: MA
authors: Kawashiri
authors: Tohru
authors: T
authors: Noguchi
authors: Atsushi
authors: A
authors: Nohara
authors: Junji
authors: J
authors: Kobayashi
authors: Junji
authors: J
authors: Koizumi
authors: Masakazu
authors: M
authors: Yamagishi
authors: Hiroshi
authors: H
authors: Mabuchi
mesh_terms: D000368:Aged; D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins