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Skipping of FCER1G Exon 2 Is Common in Human Brain But Not Associated with the Alzheimer's Disease Genetic Risk
Alyssa C Feldner1, Andrew K Turner1, James F Simpson1
1Department of Physiology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Background:
Understanding the mechanisms whereby genetic variants influence the risk of Alzheimer's disease (AD) may provide insights into treatments that could reduce AD risk.
Objective:
Here, we sought to test the hypothesis that a single nucleotide polymorphism (SNP) associated with AD risk, rs2070902, influences splicing of FCER1G exon 2.
Methods:
AD and non-AD brain samples were analyzed for FCER1G expression by genotyping, immunohistochemistry, immunofluorescence, and qPCR.
Results:
The protein encoded by FCER1G, FcRγ, is robustly expressed in microglia in both AD and non-AD brain. The FCER1G isoform lacking exon 2 (D2-FCER1G) was readily detectable. Moreover, the proportion of FCER1G expressed as this isoform was increased in brains with high AD neuropathology. However, the proportion of FCER1G expressed as the D2-FCER1G isoform was not associated with rs2070902 genotype.
Conclusions:
In summary, the proportion of FCER1G expressed as the D2-FCER1G isoform is increased with AD neuropathology but is not associated with rs2070902.
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