ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C
2014 (English)In: PROTEOMICS - Clinical Applications, ISSN 1862-8354, E-ISSN 1862-8354, Vol. 8, no 3-4, 241-250 p.Article in journal (Refereed) Published
PURPOSE: 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.
EXPERIMENTAL DESIGN: 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 AND CLINICAL RELEVANCE: 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.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2014. Vol. 8, no 3-4, 241-250 p.
Cell and Molecular Biology Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-105992DOI: 10.1002/prca.201300014ISI: 000334251600013PubMedID: 24273187OAI: oai:DiVA.org:liu-105992DiVA: diva2:712655