title: The impact of osteopontin gene variations on multiple sclerosis development and progression.
abstract: Osteopontin is a proinflammatory molecule, modulating TH1 and TH17 responses. Several reports suggest its involvement in multiple sclerosis (MS) pathogenesis. We previously reported that OPN gene variations at the 3' end are a predisposing factor for MS development and evolution. In this paper, we extended our analysis to a gene variation at the 5' end on the -156G > GG single nucleotide polymorphism (SNP) and replicated our previous findings at the 3' end on the +1239A > C SNP. We found that only +1239A > C SNP displayed a statistically significant association with MS development, but both +1239A > C and -156G > GG had an influence on MS progression, since patients homozygous for both +1239A and -156GG alleles displayed slower progression of disability and slower switch to secondary progression than those carrying +1239C and/or -156G and those homozygous for +1239A only. Moreover, patients homozygous for +1239A also displayed a significantly lower relapse rate than those carrying +1239C, which is in line with the established role of OPN in MS relapses.
authors.affiliation: Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Amedeo Avogadro, Novara, Italy. comi@med.unipmn.it
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cappellano
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Orilieri
authors.forename: Sara
authors.initials: S
authors.lastname: Buttini
authors.forename: Laura
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Franca
authors.initials: F
authors.lastname: Guerini
authors.forename: Nadia
authors.initials: N
authors.lastname: Barizzone
authors.forename: Franco
authors.initials: F
authors.lastname: Perla
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Roberto
authors.initials: R
authors.lastname: Cantello
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D053495:Osteopontin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D053495:Osteopontin