DCUN1D1 is a risk factor for frontotemporal lobar degeneration.
OBJECTIVE
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.
Villa
C
C
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy.
Venturelli
E
E
Fenoglio
C
C
Clerici
F
F
Marcone
A
A
Benussi
L
L
Gallone
S
S
Scalabrini
D
D
Cortini
F
F
Serpente
M
M
Martinelli Boneschi
F
F
Cappa
S
S
Binetti
G
G
Mariani
C
C
Rainero
I
I
Giordana
M T
MT
Bresolin
N
N
Scarpini
E
E
Galimberti
D
D
D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods; D003704:Dementia / Q000209:etiology* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012307:Risk Factors
C408631:DCUN1D1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins