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

作者：Ljunggren Stefan; Levels Johannes H M; Turkina Maria V; Sundberg Sofie; Bochem Andrea E; Hovingh Kees; Holleboom Adriaan G; Lindahl Mats; Kuivenhoven Jan Albert; Karlsson Helen^*

来源：Proteomics - Clinical Applications, 2014, 8(3-4): 241-250.

DOI：10.1002/prca.201300014

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

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.

• 出版日期2014-4