Osteopontin gene haplotypes correlate with multiple sclerosis development and progression.
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.
Chiocchetti
Annalisa
A
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.
Comi
Cristoforo
C
Indelicato
Manuela
M
Castelli
Luca
L
Mesturini
Riccardo
R
Bensi
Thea
T
Mazzarino
Maria C
MC
Giordano
Mara
M
D'Alfonso
Sandra
S
Momigliano-Richiardi
Patricia
P
Liguori
Maria
M
Zorzon
Marino
M
Amoroso
Antonio
A
Trojano
Maria
M
Monaco
Francesco
F
Leone
Maurizio
M
Magnani
Corrado
C
Dianzani
Umberto
U
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
D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin