title: Is KIF24 a genetic risk factor for Frontotemporal Lobar Degeneration?
abstract: 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, CI: 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.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Francesca
authors.initials: F
authors.lastname: Clerici
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallone
authors.forename: Diego
authors.initials: D
authors.lastname: Scalabrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fumagalli
authors.forename: Stefano
authors.initials: S
authors.lastname: Cappa
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Franceschi
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Giordana
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D016547:Kinesins