title: Three novel mutations in the apolipoprotein E gene in a sample of individuals with type 2 diabetes mellitus.
abstract: BACKGROUND
  Apolipoprotein E (apoE) is found in association with triglyceride-rich lipoproteins and is the ligand for the removal of these particles from the plasma. Genetic variations in exon 4 lead to three common gene variants: E2, E3, and E4.
  
  
  METHODS
  We performed apoE genotyping in 765 individuals with type 2 diabetes.
  
  
  RESULTS
  We identified three new variant heteroduplex patterns. Sequencing of these variants revealed three novel mutations that were related to biochemical and clinical characteristics. One mutation produced a frameshift at amino acid position 166, which predicted termination of protein synthesis. This individual had a heteroduplex pattern and sequence of E3E3, which was associated with a change in the plasma isoelectric focusing pattern and a 70% lower plasma concentration of apoE compared with healthy individuals. The other mutations were both single base changes. A CGC>CAC change at amino acid position 150 predicted a substitution of Arg>His. This individual had a heteroduplex pattern and sequence of E2E2, which was not associated with major changes in plasma lipids or apoE concentration. The third individual had a CGC>CCC base change at amino acid position 114, which predicted an Arg>Pro change. This person had a heteroduplex pattern and sequence of E3E3, higher plasma total cholesterol, and moderately decreased plasma apoE.
  
  
  CONCLUSIONS
  The frequency of new mutations in this sample (1 in 255) is higher than that of a healthy population (1 in 7900). Further screening for common apoE gene variants in individuals at risk for dyslipidemia may reveal abnormal heteroduplex patterns and uncover further mutations in this important lipid-regulating gene.
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, London WC1E 6JF, UK. rmhajst@ucl.ac.uk
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Stephens
authors.forename: M Mert
authors.initials: MM
authors.lastname: Sozen
authors.forename: Ros A
authors.initials: RA
authors.lastname: Whittall
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: Dorothy
authors.initials: D
authors.lastname: Bedford
authors.forename: Jayshree
authors.initials: J
authors.lastname: Acharya
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hurel
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007525:Isoelectric Focusing; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D001057:Apolipoproteins E