Osteopontin gene haplotypes correlate with multiple sclerosis development and progression

J Neuroimmunol. 2005 Jun;163(1-2):172-8. doi: 10.1016/j.jneuroim.2005.02.020. Epub 2005 Apr 25.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay / statistics & numerical data
  • Female
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / physiopathology
  • Osteopontin
  • RNA Stability
  • RNA, Messenger / metabolism
  • Severity of Illness Index
  • Sialoglycoproteins / blood
  • Sialoglycoproteins / genetics*
  • Up-Regulation


  • RNA, Messenger
  • SPP1 protein, human
  • Sialoglycoproteins
  • Osteopontin

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