Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Miserez, AR; Scharnagl, H; Muller, PY; Mirsaidi, R; Stähelin, HB; Monsch, A; März, W; Hoffmann, MM.
Apolipoprotein E3Basel: new insights into a highly conserved protein region.
Eur J Clin Invest. 2003; 33(8):677-685
Doi: 10.1046%2Fj.1365-2362.2003.01180.x
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- Co-Autor*innen der Med Uni Graz
- März Winfried
- Scharnagl Hubert
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- Abstract:
- BACKGROUND: Apolipoprotein E is important for the receptor-mediated uptake of triglyceride-rich lipoproteins. Mutations in the gene encoding apolipoprotein E may cause a reduced uptake of these lipoproteins. Particular apolipoprotein E mutations have been also found to be associated with nephrologic, neurologic, and even ophthalmologic diseases. Hence, a continuously expanding role in biology is being attributed to this protein. DESIGN: Randomly selected volunteers from of a large Swiss cohort were genotyped for the common apolipoprotein E isoforms (apolipoprotein E2, apolipoprotein E3, apolipoprotein E4). RESULTS: In one of the volunteers, a novel C-to-T mutation causing an alanine-to-valine substitution (A106V, designated apolipoprotein E3Basel) was discovered. Alanine at residue 106 is highly conserved between mammalian species and is located in the immediate vicinity of the 112C/R polymorphism (apolipoprotein E4). Recombinant apolipoprotein E3Basel, expressed in the baculovirus system, displayed no detectable reduction in its low density lipoprotein (LDL) receptor- and heparin-binding activities. Despite normal binding functions, apolipoprotein E3Basel might cause modifications in the lipoprotein pattern. In the index case, plasma triglycerides were elevated and in two further apolipoprotein E3Basel-carriers, cholesterol, phospholipid, apolipoprotein CIII levels, LDL-cholesterol/apoB-100- and VLDL-triglyceride/VLDL-cholesterol-ratios were higher compared with apolipoprotein E3Basel-noncarriers when pair-matched for age and gender. One of the four apolipoprotein E3Basel-carriers from the index family had a personal history of Alzheimer's disease. CONCLUSIONS: Alanine at amino acid position 106 is highly conserved but not crucial in the receptor-mediated uptake of lipoprotein particles. Nevertheless, amino acid position 106 might be involved in the apolipoprotein E-dependent regulation of the lipoprotein lipase that hydrolyzes triglycerides and in the development of Alzheimer's disease.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Apolipoprotein E3 -
- Apolipoproteins E - genetics
- Cholesterol - analysis
- Crystallography, X-Ray - analysis
- Female - analysis
- Heparin - metabolism
- Humans - metabolism
- Lipoproteins - analysis
- Male - analysis
- Middle Aged - analysis
- Mutation - genetics
- Pedigree - genetics
- Phenotype - genetics
- Phospholipids - analysis
- Receptors, LDL - analysis
- Triglycerides - analysis
- Find related publications in this database (Keywords)
- Alzheimer's disease
- apolipoprotein E
- binding
- hypertriglyceridaemia
- low-density receptor
- mutation