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OP0093 Interferon gamma gene polymorphism: Relationship to susceptibility and severity of rheumatoid arthritis in a prospective study
  1. A Constantin1,2,3,
  2. F Navaux2,
  3. V Lauwers-Cancès1,
  4. M Abbal3,
  5. JP Van Meerjwijk4,
  6. B Mazières2,
  7. A Cambon-Thomsen1,
  8. A Cantagrel1,3
  1. 1Rheumatology Service, Rangueil Hospital, Toulouse, France
  2. 2INSERM, Unité 558, Toulouse, France
  3. 3Immunology Service, Rangueil Hospital, INSERM Unité 395, Toulouse, France
  4. 4

Abstract

Background Interferon gamma (IFNg) is a multifunctional cytokine that plays an important role in modulating most of the phases of the immune and inflammatory responses. IFNg gene is a potential candidate as marker of rheumatoid arthritis (RA) susceptibility and severity.

Objectives In this prospective longitudinal study we have investigated the association between a variable length CA repeat in the first intron of the IFNg gene and RA susceptibility and severity.

Methods One hundred and three early (< 1 year) RA patients (ACR 1987 criteria) were evaluated clinically, serologically and radiographically (modified Sharp/van der Heijde method) yearly for 4 years. The total radiological damage score was used to quantify RA severity after 4 years of follow-up. One hundred thirty unrelated healthy individuals were used as controls. The microsatellite region in the first intron of the IFNg gene was analysed by PCR and electrophoresis in an automatic DNA sequencer.

Results Characteristics of the 103 RA patients at inclusion were as follows: 80 females, 23 males, mean age 49.4 ± 15.5 years, mean disease duration 6.9 ± 3.7 months, mean tender joint score 12.4 ± 8.9, mean swollen joint number 6 ± 6.2, mean erythrocyte sedimentation rate 29.8 ± 25.2, rheumatoid factor positive (ELISA method) 71/103, mean radiological score 5 ± 13.6. The allele sizes of the IFNg gene polymorphic region ranged from 122 bp (11 CA repeats) to 134 bp (17 CA repeats). Twelve CA repeat (12R) and thirteen CA repeat (13R) alleles were the most common in RA patients (respectively 41.7% and 48.5%) and healthy controls (respectively 45.3% and 45.7%). 12R/12R, 12R/13R and 13R/13R genotypes were the most common in RA patients (respectively 15.6%, 44.1% and 21.6%) and healthy controls (respectively 22.4%, 38.0% and 21.7%). No association has been observed between the IFNg gene polymorphism and RA susceptibility or severity.

Conclusion Although the present study fails to reveal any association between this particular IFNg gene polymorphism and RA, the search for RA susceptibility and severity genes remains an important issue to better understand RA pathophysiology and to optimise the strategies for treatment of early RA.

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