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DCUN1D1 is a risk factor for frontotemporal lobar degeneration.
C Villa1, E Venturelli, C Fenoglio
1Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy.
European Journal of Neurology
|May 29, 2009
Summary
The GG genotype of the DCUN1D1 rs4859146 single nucleotide polymorphism (SNP) is a risk factor for frontotemporal lobar degeneration (FTLD). This finding suggests a potential role for protein degradation pathways in FTLD pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Frontotemporal lobar degeneration (FTLD) is a proteinopathy.
- Genes involved in protein misfolding and degradation may influence FTLD pathogenesis.
Purpose of the Study:
- To investigate the association between the DCUN1D1 gene, involved in protein degradation, and FTLD.
- To explore the role of DCUN1D1 single nucleotide polymorphisms (SNPs) in FTLD development.
Main Methods:
- An association study was conducted comparing 220 FTLD patients with 229 age-matched controls.
- Genotyping of the DCUN1D1 rs4859146 and rs4859147 SNPs was performed.
Main Results:
- The GG genotype of the DCUN1D1 rs4859146 SNP showed a significantly increased frequency in FTLD patients (6.9%) compared to controls (1.7%).
- This association was significant for the behavioral variant of FTD and progressive aphasia subtypes.
- No significant differences were found for the DCUN1D1 rs4859147 SNP.
Conclusions:
- The GG genotype of the DCUN1D1 rs4859146 SNP is a risk factor for FTLD.
- This genetic variant increases the risk of developing FTLD approximately fourfold.
- DCUN1D1 rs4859146 SNP may contribute to FTLD pathogenesis through its role in protein degradation.
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