TY - JOUR
T1 - GSK3β genetic variability in patients with Multiple Sclerosis
AU - Galimberti, Daniela
AU - MacMurray, James
AU - Scalabrini, Diego
AU - Fenoglio, Chiara
AU - De Riz, Milena
AU - Comi, Cristoforo
AU - Comings, David
AU - Cortini, Francesca
AU - Villa, Chiara
AU - Serpente, Maria
AU - Cantoni, Claudia
AU - Ridolfi, Elisa
AU - Fardipoor, Ma Hin
AU - Leone, Maurizio
AU - Monaco, Francesco
AU - Bresolin, Nereo
AU - Scarpini, Elio
N1 - Funding Information:
This work was supported by grants from Italian Ministry of Health (Giovani Ricercatori 2007, D.lgs 502/92), and Ing. Cesare Cusan.
PY - 2011/6/15
Y1 - 2011/6/15
N2 - 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.
AB - 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.
KW - GSK3β
KW - Multiple Sclerosis
KW - Polymorphism
KW - Risk factor
UR - http://www.scopus.com/inward/record.url?scp=79956047743&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2011.04.024
DO - 10.1016/j.neulet.2011.04.024
M3 - Article
C2 - 21527318
AN - SCOPUS:79956047743
SN - 0304-3940
VL - 497
SP - 46
EP - 48
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -