title: Resequencing the APOE gene reveals that rare mutations are not significant contributory factors in the development of type III hyperlipidemia.
abstract: BACKGROUND
  APOE (apolipoprotein E gene) 2/2 genotype and an apolipoprotein B/total cholesterol (ApoB/TC) ratio <0.15 are diagnostic for type III hyperlipidemia. We hypothesized that patients with APOE genotype 2/3 or 2/4 and an ApoB/TC ratio <0.15 may have a mutation in their epsilon 3 or 4 allele, resulting in a type III hyperlipidemia phenotype.
  
  
  OBJECTIVE
  We tested this hypothesis.
  
  
  METHODS
  The DNA sequence of all 4 exons and exon/intron boundaries of the APOE (plus 600 bp upstream of exon 1) of 47 patients with APOE 2/3 and 18 patients with APOE 2/4 genotype and an ApoB/TC ratio <0.15 was determined. As controls the APOE sequence of 53 APOE genotype 2/3 and 20 APOE genotype 2/4 probands with ApoB/TC ratio >0.15 was determined. The sequence analysis was extended to include 47 patients with APOE genotype 3/3, 14 with APOE genotype 3/4, and 3 with APOE genotype 4/4 and an ApoB/TC ratio <0.15. Finally, we determined the sequence of the APOE gene in 145 patients with an ApoB/TC ratio >0.15 and who had triglycerides above the 90th percentile for age and sex.
  
  
  RESULTS
  No deleterious variants in the APOE gene were observed in patients with APOE genotype other than 2/2 and an ApoB/TC ratio <0.15. Only a single probably deleterious variant, K72E, was observed in patients with triglycerides above the 90th percentile.
  
  
  CONCLUSIONS
  Patients with an ApoB/TC ratio <0.15 do not have an increased likelihood of mutation in the APOE gene, and rare variants in the APOE gene are not important in the development of hypertriglyceridemia.
authors: Endokrinologie und Stoffwechsel, Medizinische Klinik III, Zentrum für Innere Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: evans@uke.uni-hamburg.de.
authors: David
authors: D
authors: Evans
authors: Frank Ulrich
authors: FU
authors: Beil
authors: Jens
authors: J
authors: Aberle
mesh_terms: D000328:Adult; D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D001057:Apolipoproteins E; D014280:Triglycerides
keywords: APOE rare variants; Dyslipidemia; Hypertriglyceridemia; Resequencing; Type III hyperlipidemia