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Friday, Mar.29, 2024
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miRNA: |
hsa-miR-659 |
Disease: |
frontotemporal dementia |
Relationship type: |
Causal |
Detection method for miRNA expression: |
Northern blot, qRT-PCR etc |
Expression pattern of miRNA: |
normal |
Validated targets of miRNA from the reference: |
GRN |
Validated targets of miRNA from TarBase: |
unknown : More... |
Predicted targets: |
MIRANDA, TARGETSCAN, PICTAR-VERT |
Description: Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3'untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared to homozygous C-allele carriers (95% CI: 1.50-6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. |
Reference:
Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia.
| PMID:18723524
Rademakers R, Eriksen JL, Baker M, Robinson T, Ahmed Z, Lincoln SJ, Finch N, Rutherford NJ, Crook RJ, Josephs KA, Boeve BF
Hum Mol Genet. 2008 Aug 22. [Epub ahead of print] |
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