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Apolipoprotein E3 Basel : new insights into a highly conserved protein region
Author(s) -
Miserez A. R.,
Scharnagl H.,
Muller P. Y.,
Mirsaidi R.,
Stähelin H. B.,
Monsch A.,
März W.,
Hoffmann M. M.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01180.x
Subject(s) - apolipoprotein b , apolipoprotein c2 , very low density lipoprotein , apolipoprotein e , lipoprotein , ldl receptor , medicine , cholesterol , biology , endocrinology , biochemistry , chemistry , disease
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 E3 Basel ) 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 E3 Basel , 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 E3 Basel might cause modifications in the lipoprotein pattern. In the index case, plasma triglycerides were elevated and in two further apolipoprotein E3 Basel ‐carriers, cholesterol, phospholipid, apolipoprotein CIII levels, LDL‐cholesterol/apoB‐100‐ and VLDL‐triglyceride/VLDL‐cholesterol‐ratios were higher compared with apolipoprotein E3 Basel ‐noncarriers when pair‐matched for age and gender. One of the four apolipoprotein E3 Basel ‐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.