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ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C

Ljunggren, S., Levels, J. H. M., Turkina, M. V., Sundberg, S., Bochem, A. E., Hovingh, K., Holleboom, A. G., Lindahl, M., Kuivenhoven, J. A. & Karlsson, H., Apr-2014, In : Proteomics. Clinical Applications. 8, 3-4, p. 241-250 10 p.

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  • ApoA-I mutations, L202P and K131del, in HDL from heterozygotes

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DOI

  • Stefan Ljunggren
  • Johannes H. M. Levels
  • Maria V. Turkina
  • Sofie Sundberg
  • Andrea E. Bochem
  • Kees Hovingh
  • Adriaan G. Holleboom
  • Mats Lindahl
  • Jan Albert Kuivenhoven
  • Helen Karlsson

PurposeMutations 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 designPlasma 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.

ResultsApoA-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--2-glycoprotein while HDL from the apoA-I-K131del heterozygotes contained more alpha-1-antitrypsin and transthyretin.

Conclusions and clinical relevanceBoth 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.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalProteomics. Clinical Applications
Volume8
Issue number3-4
Publication statusPublished - Apr-2014

    Keywords

  • ApoA-I-K131del, ApoA-I-L202P, Apolipoprotein A-I, 2DE, High-density lipoprotein, HIGH-DENSITY-LIPOPROTEIN, APOLIPOPROTEIN-A-I, LECITHIN-CHOLESTEROL ACYLTRANSFERASE, CORONARY-ARTERY-DISEASE, MASS-SPECTROMETRY, SR-BI, PROTEIN, ATHEROSCLEROSIS, ACTIVATION, EFFLUX

ID: 16390867