title: Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism.
abstract: BACKGROUND
  Alleles of apolipoprotein E (APOE) are the major genetic risk factor for late onset Alzheimer's Disease (LOAD). Recently, an APOE splice variant that retains intron 3 (APOE-I3) was identified. To gain insight into the possible role of this isoform in LOAD, we quantified its expression in a cohort of 56 human brain specimens by using quantitative RT-PCR.
  
  
  RESULTS
  We found that APOE-I3 generally represents a low percentage (< 0.5%) of overall APOE expression. However, in one specimen, the proportion of APOE-I3 was increased about ~13 fold. This specimen was unique in the cohort for possessing the minor allele of an intron 3 single nucleotide polymorphism (SNP), rs12982192. Additionally, an allelic expression imbalance study indicated that the rs12982192 minor allele was associated with increased APOE-I3 expression.
  
  
  CONCLUSIONS
  Overall, we interpret our results as suggesting that APOE-I3 represents a minor portion of APOE expression and that rs12982192 is associated with APOE intron 3 retention. Since the minor allele of this SNP is on the same haplotype as the minor allele of rs429358, which defines the APOE4 allele, we speculate that rs12982192 may reflect a modest loss of mRNA encoding functional APOE4.
authors.affiliation: Department of Physiology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. steve.estus@uky.edu.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Dieter
authors.forename: Steven
authors.initials: S
authors.lastname: Estus
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