Journal
NEUROSCIENCE LETTERS
Volume 482, Issue 3, Pages 240-244Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2010.07.047
Keywords
KIF24; UBAP1; Polymorphism; Frontotemporal Lobar Degeneration (FTLD); Risk factor; Neurodegeneration; Frontotemporal Dementia
Categories
Funding
- Monzino Foundation
- IRCCS Ospedale Maggiore Milano, Associazione per la Ricerca sulle Demenze (ARD)
- Programma Strategico RF 2007 [conv. PS39]
- Italian Ministry of Health
- Progetto Regione Lombardia Delibera [VIII/008724]
- Ing. Cesare Cusan
Ask authors/readers for more resources
Linkage analysis identified a region on chromosome 9p associated with Frontotemporal Lobar Degeneration (FTLD). A detailed analysis of candidate genes lying in this region demonstrated an association with Ubiquitin Associated Protein (UBAP)1. The distribution of five Single Nucleotide Polymorphisms (SNPs) located in the chromosome 9 haplotype identified via linkage analysis, including UBAP1 rs7018487, UBAP2 rs1785506 and rs307658, and KIF24 rs17350674 and rs10814083, has been determined in a population of 284 patients diagnosed with FTLD, including 245 with behavioural variant Frontotemporal Dementia (bvFTD), 23 with Progressive Aphasia and 16 with Semantic Dementia, compared with 318 age-matched controls. A statistically significant increased frequency of the KIF24 rs17350674 AA genotype was observed in patients compared with controls (7.4 versus 2.5%; P = 0.0068, OR: 3.63, CI: 1.58-8.35). Considering each syndrome separately, similar results where obtained in bvFTD versus controls (7.7 versus 2.5%, P = 0.005, OR: 3.26, CI: 1.40-7.57). Stratifying for gender, a statistically significant increased genotypic frequency was observed in female patients as compared with female controls (8.9 versus 2.5%, P = 0.008, OR: 3.85, Cl: 1.36-10.93). In silico analysis predicted that the substitution from W to L caused by the rs17350674 affects protein function (P < 0.05). The KIF24 rs17350674 polymorphism likely acts as a risk factor for sporadic FTLD, but a replication study would be needed to confirm these preliminary findings. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available