GSK3β genetic variability in patients with Multiple Sclerosis

Document Type

Article

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.

Medical Subject Headings

Female; Genetic Predisposition to Disease; Genotype; Glycogen Synthase Kinase 3 (genetics); Glycogen Synthase Kinase 3 beta; Humans; Male; Middle Aged; Multiple Sclerosis (genetics); Polymorphism, Single Nucleotide

Publication Date

6-15-2011

Publication Title

Neuroscience letters

E-ISSN

1872-7972

Volume

497

Issue

1

First Page

46

Last Page

8

PubMed ID

21527318

Digital Object Identifier (DOI)

10.1016/j.neulet.2011.04.024

Link to Full Text

Share

COinS