title: Osteopontin gene haplotypes correlate with multiple sclerosis development and progression.
abstract: Osteopontin (OPN) is an inflammatory cytokine highly expressed in multiple sclerosis (MS) plaques. In a previous work, we showed that four OPN polymorphisms form three haplotypes (A, B, and C) and that homozygotes for haplotype-A display lower OPN levels than non-AA subjects. In this work, we evaluated the distribution of these OPN haplotypes in 425 MS patients and 688 controls. Haplotype-A homozygotes had about 1.5 lower risk of developing MS than non-AA subjects. Clinical analysis of 288 patients showed that AA patients displayed slower switching from a relapsing remitting to a secondary progressive form and milder disease with slower evolution of disability. MS patients displayed increased OPN serum levels, which were partly due to the increased frequency of non-AA subjects. Moreover in AA patients, OPN levels were higher than in AA controls and similar to those found in both non-AA patients and controls, which suggests a role of the activated immune response. These data suggest that OPN genotypes may influence MS development and progression due to their influence on OPN levels.
authors.affiliation: Interdisciplinary Research Center of Autoimmune Diseases (IRCAD) and Department of Medical Sciences, A. Avogadro University of Eastern Piedmont, via Solaroli 17, I-28100 Novara, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.forename: Manuela
authors.initials: M
authors.lastname: Indelicato
authors.forename: Luca
authors.initials: L
authors.lastname: Castelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Mesturini
authors.forename: Thea
authors.initials: T
authors.lastname: Bensi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mazzarino
authors.forename: Mara
authors.initials: M
authors.lastname: Giordano
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Patricia
authors.initials: P
authors.lastname: Momigliano-Richiardi
authors.forename: Maria
authors.initials: M
authors.lastname: Liguori
authors.forename: Marino
authors.initials: M
authors.lastname: Zorzon
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.forename: Francesco
authors.initials: F
authors.lastname: Monaco
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.forename: Corrado
authors.initials: C
authors.lastname: Magnani
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D000328:Adult; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000706:statistics & numerical data; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000503:physiopathology; D053495:Osteopontin; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000097:blood / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin