title: ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C.
abstract: OBJECTIVE
  Mutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations, apoA-I(L202P) and apoA-I(K131del) , are present on plasma HDL particles derived from heterozygote carriers and whether this is associated to changes in HDL protein composition.
  
  
  METHODS
  Plasma HDL of heterozygotes for either apoA-I(L202P) or apoA-I(K131del) and family controls was isolated using ultracentrifugation. HDL proteins were separated by 2DE and analyzed by MS.
  
  
  RESULTS
  ApoA-I peptides containing apoA-I(L202P) or apoA-I(K131del) were identified in HDL from heterozygotes. The apoA-I(L202P) mutant peptide was less abundant than wild-type peptide while the apoA-I(K131del) mutant peptide was more abundant than wild-type peptide in the heterozygotes. Two-dimensional gel electrophoresis analyses indicated that, compared to controls, HDL in apoA-I(L202P) carriers contained less apoE and more zinc-α-2-glycoprotein while HDL from the apoA-I(K131del) heterozygotes contained more alpha-1-antitrypsin and transthyretin.
  
  
  CONCLUSIONS
  Both apoA-I(L202P) and apoA-I(K131del) were identified in HDL. In heterozygotes, these mutations have markedly differential effects on the concentration of wild-type apoA-I in the circulation, as well as the HDL proteome, both of which might affect the clinical phenotype encountered in the heterozygous carriers.
authors.affiliation: Occupational and Environmental Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ljunggren
authors.forename: Johannes H M
authors.initials: JH
authors.lastname: Levels
authors.forename: Maria V
authors.initials: MV
authors.lastname: Turkina
authors.forename: Sofie
authors.initials: S
authors.lastname: Sundberg
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Bochem
authors.forename: Kees
authors.initials: K
authors.lastname: Hovingh
authors.forename: Adriaan G
authors.initials: AG
authors.lastname: Holleboom
authors.forename: Mats
authors.initials: M
authors.lastname: Lindahl
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Helen
authors.initials: H
authors.lastname: Karlsson
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood*; D015180:Electrophoresis, Gel, Two-Dimensional; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011228:Prealbumin / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000097:blood; D000090203:Zn-Alpha-2-Glycoprotein; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D011228:Prealbumin; C043392:SERPINA1 protein, human; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein; D000515:alpha 1-Antitrypsin
keywords: 2DE; ApoA-IK131del; ApoA-IL202P; Apolipoprotein A-I; High-density lipoprotein