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THU0009 Fibronectin gene polymorphism in severe and mild rheumatoid arthritis
  1. M Fabris,
  2. S Sacco,
  3. E Di Poi,
  4. G Favret,
  5. GF Ferraccioli
  1. Division of Rheumatology-DPMSC, University of Udine, Udine, Italy


Background The importance of Fibronectin (Fn) in RA chronic synovial inflammation is increasing. There are at least 6 restriction fragment length polymorphisms (RFLPs) described so far in the Fn gene, but very few is known about their possible functional relevance.

Objectives In this study we assessed the role of the Msp-I Fn gene polymorphism in a series of patients with severe aggressive disease who were treated with anti-TNF-α therapy because of their poor response to a DMARDs combination strategy. The phenotype of these patients were compared to those of a cohort of patients who had a good response to Methotrexate (MTX), thus revealing a mild/moderate disease.

Methods Seventy-nine (79) RA patients and sixty-one (61) controls (Healthy Blood Donors, HBD) entered the study. RA patients were split into 2 subgroups: 57 rheumatoids in stable partial remission (less than 3 swollen joints and a morning stiffness of less than 20’) since at least six months after MTX treatment (15 mg/w weekly, range 10–25 mg/w), thus called MTX-responders (MTX-R) and 22 rheumatoids with still active disease (more than 6 swollen joints and a morning stiffness of at least 60’) despite 6 months of combination therapy (MTX + Sulphasalazine + Hydroxychloquine or MTX + Cyclosporine, including low doses of prednisone, 5 mg/day). This latter group received anti-TNF-α therapy and was then labelled anti-TNF-treated (TNF-T). Genotyping for the Msp-I Fn gene polymorphism was made according to Avila et al.,1 who named C the allele resistant to enzyme’s digestion and D the variant susceptible. Statistical analyses (Odds Ratio, 95% Confidence Interval) were performed using Prism software (Graph-Pad, S. Diego, CA 92121-USA).

Results MTX-R had an overall frequency of DD homozygousity of 56.1% vs 52.5% in HBD, while in TNF-T subgroup the DD genotype had a frequency of 81.8% (OR = 4.1, CI = 1.2–13, p = 0.008 vs HBD). The comparison between TNF-T and MTX-R is similarly striking (OR = 3.5, CI = 1.1–12, p = 0.01).

Conclusion The DD genotype for Msp-I Fn gene polymorphism marks the patients who received anti-TNF-α therapy and may lead to a more aggressive phenotype in RA.


  1. Avila JJ, et al. Am J Respir Cell Mol Biol. 1999;20:106

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