A novel polymorphism in SEL1L confers susceptibility to Alzheimer's disease.
Alzheimer's disease (AD) is considered to be a conformational disease arising from the accumulation of misfolded and unfolded proteins in the endoplasmic reticulum (ER). SEL1L is a component of the ER stress degradation system, which serves to remove unfolded proteins by retrograde degradation using the ubiquitin-proteosome system. In order to identify genetic variations possibly involved in the disease, we analysed the entire SEL1L gene sequence in Italian sporadic AD patients. Here we report on the identification of a new polymorphism within the SEL1L intron 3 (IVS3-88 A>G), which contains potential binding sites for transcription factors involved in ER-induced stress. Our statistical analysis shows a possible role of the novel polymorphism as independent susceptibility factor of Alzheimer's dementia.
Saltini
Giuliana
G
Department of Sciences and Biomedical Technologies, University of Milan Via F.lli Cervi 93, 20090 Segrate-Milan, Italy.
Dominici
Roberto
R
Lovati
Carlo
C
Cattaneo
Monica
M
Michelini
Stefania
S
Malferrari
Giulia
G
Caprera
Andrea
A
Milanesi
Luciano
L
Finazzi
Dario
D
Bertora
Pierluigi
P
Scarpini
Elio
E
Galimberti
Daniela
D
Venturelli
Eliana
E
Musicco
Massimo
M
Adorni
Fulvio
F
Mariani
Claudio
C
Biunno
Ida
I
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*
D011506:Proteins; C117384:SEL1L protein, human