RGD Reference Report - Common variant in GRN is a genetic risk factor for hippocampal sclerosis in the elderly. - Rat Genome Database

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Common variant in GRN is a genetic risk factor for hippocampal sclerosis in the elderly.

Authors: Dickson, DW  Baker, M  Rademakers, R 
Citation: Dickson DW, etal., Neurodegener Dis. 2010;7(1-3):170-4. Epub 2010 Mar 3.
RGD ID: 5509600
Pubmed: PMID:20197700   (View Abstract at PubMed)
PMCID: PMC2859236   (View Article at PubMed Central)
DOI: DOI:10.1159/000289231   (Journal Full-text)

BACKGROUND: Hippocampal sclerosis (HpScl) is common in elderly subjects with dementia, either alone or accompanied by other pathologic processes. It is also found in >70% of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP). TDP-43 inclusions are detected in >20% of Alzheimer disease (AD) and >70% of HpScl cases. The most common cause of FTLD-TDP is mutation in the progranulin gene (GRN). Recently, a common genetic variant in the 3' untranslated region (3'UTR) of GRN (rs5848; c.*78C>T) located in a microRNA binding site regulated progranulin expression, and the T-allele was increased in FTLD-TDP compared to controls. OBJECTIVE: The goal of this study was to determine if the 3'UTR variant in GRN was associated with TDP-43 immunoreactivity in AD with and without HpScl. METHODS: 644 cases of pathologically confirmed AD, including 57 with HpScl, were screened for TDP-43 immunoreactivity and were genotyped at the GRN 3'UTR single-nucleotide polymorphism rs5848 using previously published methods. RESULTS: There was a trend (p = 0.06) for TDP-43 immunoreactivity, but a very significant (p = 0.005) association of HpScl with the variant, with 72% of AD with HpScl carrying a T-allele, compared to 51% of AD without HpScl carrying a T-allele. CONCLUSION: The results suggest that a genetic variant in GRN leading to decreased levels of progranulin may be a risk factor for HpScl in AD, while its role in TDP-43 immunoreactivity in AD remains less certain.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IAGP 5509600DNA:SNP:3'UTR:rs5848(human)RGD 
Alzheimer's disease  ISOGRN (Homo sapiens)5509600; 5509600DNA:SNP:3'UTR:rs5848(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Grn  (granulin precursor)

Genes (Mus musculus)
Grn  (granulin)

Genes (Homo sapiens)
GRN  (granulin precursor)


Additional Information