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

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


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
Issue number3-4
Publication statusPublished - Apr-2014


  • ApoA-I-K131del
  • ApoA-I-L202P
  • Apolipoprotein A-I
  • 2DE
  • High-density lipoprotein
  • SR-BI

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