GSK3β genetic variability in patients with Multiple Sclerosis

Daniela Galimberti, James MacMurray, Diego Scalabrini, Chiara Fenoglio, Milena De Riz, Cristoforo Comi, David Comings, Francesca Cortini, Chiara Villa, Maria Serpente, Claudia Cantoni, Elisa Ridolfi, Ma Hin Fardipoor, Maurizio Leone, Francesco Monaco, Nereo Bresolin, Elio Scarpini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)46-48
Number of pages3
JournalNeuroscience Letters
Volume497
Issue number1
DOIs
Publication statusPublished - Jun 15 2011

Keywords

  • GSK3β
  • Multiple Sclerosis
  • Polymorphism
  • Risk factor

ASJC Scopus subject areas

  • Neuroscience(all)

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