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

doi:10.1016/j.neulet.2011.04.024

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

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer 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.

Lingua originale	Inglese
pagine (da-a)	46-48
Numero di pagine	3
Rivista	Neuroscience Letters
Volume	497
Numero di pubblicazione	1
DOI	https://doi.org/10.1016/j.neulet.2011.04.024
Stato di pubblicazione	Pubblicato - 15 giu 2011
Pubblicato esternamente	Sì

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10.1016/j.neulet.2011.04.024

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Galimberti, D., MacMurray, J., Scalabrini, D., Fenoglio, C., De Riz, M., Comi, C., Comings, D., Cortini, F., Villa, C., Serpente, M., Cantoni, C., Ridolfi, E., Fardipoor, M. H., Leone, M., Monaco, F., Bresolin, N., & Scarpini, E. (2011). GSK3β genetic variability in patients with Multiple Sclerosis. Neuroscience Letters, 497(1), 46-48. https://doi.org/10.1016/j.neulet.2011.04.024

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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.",

keywords = "GSK3β, Multiple Sclerosis, Polymorphism, Risk factor",

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

note = "Funding Information: This work was supported by grants from Italian Ministry of Health (Giovani Ricercatori 2007, D.lgs 502/92), and Ing. Cesare Cusan.",

year = "2011",

month = jun,

day = "15",

doi = "10.1016/j.neulet.2011.04.024",

language = "English",

volume = "497",

pages = "46--48",

journal = "Neuroscience Letters",

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Galimberti, D, MacMurray, J, Scalabrini, D, Fenoglio, C, De Riz, M, Comi, C, Comings, D, Cortini, F, Villa, C, Serpente, M, Cantoni, C, Ridolfi, E, Fardipoor, MH, Leone, M, Monaco, F, Bresolin, N & Scarpini, E 2011, 'GSK3β genetic variability in patients with Multiple Sclerosis', Neuroscience Letters, vol. 497, n. 1, pagg. 46-48. https://doi.org/10.1016/j.neulet.2011.04.024

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

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U2 - 10.1016/j.neulet.2011.04.024

DO - 10.1016/j.neulet.2011.04.024

M3 - Article

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VL - 497

SP - 46

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JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 1

ER -

GSK3β genetic variability in patients with Multiple Sclerosis

Abstract

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