Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism.
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.
Dieter
Laura S
LS
Department of Physiology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. steve.estus@uky.edu.
Estus
Steven
S
Neuron. 2009 Aug 13;63(3):287-303
19679070
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
12184808
J Clin Invest. 1985 Oct;76(4):1501-13
3932467
Biochim Biophys Acta. 1987 Jan 13;917(1):148-61
3539206
BMC Mol Biol. 2005 Feb 18;6:4
15720708
J Neuropathol Exp Neurol. 2009 Jan;68(1):1-14
19104448
Nat Rev Neurosci. 2009 May;10(5):333-44
19339974
J Neurosci. 2006 May 10;26(19):4985-94
16687490
Mol Neurodegener. 2009 Nov 04;4:46
19889229
Neurosci Lett. 1999 Sep 10;272(2):83-6
10507547
J Neurosci. 2001 Feb 1;21(3):812-22
11157067
J Neurosci. 2008 Feb 6;28(6):1452-9
18256266
Hum Mol Genet. 2008 Apr 1;17(7):929-35
18065781
Hum Mol Genet. 2010 Jan 1;19(1):122-34
19825846
Exp Neurol. 1997 Feb;143(2):313-8
9056393