title: Apolipoprotein E3Basel: new insights into a highly conserved protein region.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine, University Hospital Bruderholz, Switzerland. andre-r.miserez@unibas.ch
authors.forename: A R
authors.initials: AR
authors.lastname: Miserez
authors.forename: H
authors.initials: H
authors.lastname: Scharnagl
authors.forename: P Y
authors.initials: PY
authors.lastname: Muller
authors.forename: R
authors.initials: R
authors.lastname: Mirsaidi
authors.forename: H B
authors.initials: HB
authors.lastname: Stähelin
authors.forename: A
authors.initials: A
authors.lastname: Monsch
authors.forename: W
authors.initials: W
authors.lastname: März
authors.forename: M M
authors.initials: MM
authors.lastname: Hoffmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000032:analysis; D018360:Crystallography, X-Ray; D005260:Female; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D010743:Phospholipids / Q000032:analysis; D011973:Receptors, LDL / Q000032:analysis; D014280:Triglycerides / Q000032:analysis
chemical_list: D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008074:Lipoproteins; D010743:Phospholipids; D011973:Receptors, LDL; D014280:Triglycerides; D006493:Heparin; D002784:Cholesterol