DCUN1D1 is a risk factor for frontotemporal lobar degeneration

C. Villa, E. Venturelli, C. Fenoglio, F. Clerici, A. Marcone, L. Benussi, S. Gallone, D. Scalabrini, F. Cortini, M. Serpente, F. Martinelli Boneschi, S. Cappa, G. Binetti, C. Mariani, I. Rainero, M. T. Giordana, N. Bresolin, E. Scarpini, D. Galimberti

Research output: Contribution to journalArticlepeer-review


Background and purpose: Frontotemporal lobar degeneration (FTLD) is considered as a proteinopathy; therefore, it is conceivable that genes encoding for factors involved in protein misfolding and/or degradation could play a role in its pathogenesis. Methods: An association study of defective in cullin neddylation 1 (DCN-1)-domain containing 1 (DCUN1D1), which is involved in protein degradation, was carried out in a population of 220 patients with FTLD as compared with 229 age-matched controls. Results: A statistically significant increased frequency of the GG genotype of the DCUN1D1 rs4859146 single nucleotide polymorphism (SNP) was observed in patients compared with controls (6.9 vs. 1.7%, P = 0.011, adjusted OR: 4.39, 95% CI: 1.40-13.78). Stratifying according to the clinical syndrome, significant differences were observed between the behavioral variant of frontotemporal dementia and controls (GG frequency: 6.3 vs. 1.7%, P = 0.02, OR:4.0, 95%, CI = 1.24-12.92), as well as between patients with progressive aphasia compared with controls (15.4 vs. 1.7%, P = 0.014, OR = 11.30, 95%, CI = 1.63-78.45), but not in patients with SD versus controls (8.3 vs. 1.7%, P = 0.18, OR = 5.24, 95% C.I. = 0.45-60.63). No significant differences in allelic and genotypic frequencies of the DCUN1D1 rs4859147 SNP were found. Conclusions: The GG genotype of the DCUN1D1 rs4859147 SNP represents a risk factor for the development of FTLD, increasing the risk of about fourfold.

Original languageEnglish
Pages (from-to)870-873
Number of pages4
JournalEuropean Journal of Neurology
Issue number7
Publication statusPublished - Jul 2009


  • DCUN1D1
  • Frontotemporal lobar degeneration
  • Polymorphism
  • Risk factor

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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