title: GSK3β genetic variability in patients with Multiple Sclerosis.
abstract: Glycogen synthase kinase-3 beta (GSK3β) is a ubiquitous kinase that is part of multiple signaling pathways. It has neurotrophic/neuroprotective effects by mediating the actions of neurotrophic molecules in the brain, thus providing neuroprotection through modulation of energy metabolism. Notably, it has been demonstrated that GSK3β is involved in Wnt-beta-catenin signaling, which contributes to the inhibition of myelination and remyelination processes in mammals. Three-hundred nineteen patients with MS and 294 age-matched controls were genotyped by allelic discrimination for four common GSK3β variants (rs2199503, rs9826659, rs334558 and rs6438552) tagging about 100% of GSK-3β variability. A statistically significant increased frequency of the rs334558 GG genotype was observed in patients as compared with controls (25.4% versus 17.7%, P=0.02; OR:1.58, 95%CI: 1.07-2.34). Stratifying MS patients according to the disease subtype, a statistically significant difference of rs334558 GG frequency was found between Relapsing Remitting (RR), but not Primary Progressive or Secondary MS, and controls (27.0% versus 17.7%, P=0.01; OR: 1.72, 95%CI: 1.13-2.61). GSK3β rs334558 is a susceptibility factor for MS. As it is located in the promoter region, a possible explanatory mechanism could be an influence of the variant on the gene transcription rate.
authors.affiliation: Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. daniela.galimberti@unimi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: James
authors.initials: J
authors.lastname: Macmurray
authors.forename: Diego
authors.initials: D
authors.lastname: Scalabrini
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Milena
authors.initials: M
authors.lastname: De Riz
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.forename: David
authors.initials: D
authors.lastname: Comings
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Ridolfi
authors.forename: Ma-Hin
authors.initials: MH
authors.lastname: Fardipoor
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.forename: Francesco
authors.initials: F
authors.lastname: Monaco
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3