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<p>Abstract</p> <p>Background</p> <p>Alleles of apolipoprotein E (<it>APOE</it>) are the major genetic risk factor for late onset Alzheimer's Disease (LOAD). Recently, an <it>APOE </it>splice variant that retains intron 3 (<it>APOE-I3</it>) 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.</p> <p>Results</p> <p>We found that <it>APOE-I3 </it>generally represents a low percentage (< 0.5%) of overall <it>APOE </it>expression. However, in one specimen, the proportion of <it>APOE-I3 </it>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 <it>APOE-I3 </it>expression.</p> <p>Conclusions</p> <p>Overall, we interpret our results as suggesting that <it>APOE-I3 </it>represents a minor portion of <it>APOE </it>expression and that rs12982192 is associated with <it>APOE </it>intron 3 retention. Since the minor allele of this SNP is on the same haplotype as the minor allele of rs429358, which defines the <it>APOE</it>4 allele, we speculate that rs12982192 may reflect a modest loss of mRNA encoding functional <it>APOE</it>4.</p>