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Rheumatoid arthritis and genetic markers in Syrian and French populations: different effect of the shared epitope
  1. Leyla Kazkaz1,
  2. Hubert Marotte2,
  3. Mayassa Hamwi2,
  4. Marie Angélique Cazalis2,
  5. Pascal Roy3,
  6. Bruno Mougin2,
  7. Pierre Miossec2
  1. 1Teshreen Hospital, Damascus, Syria
  2. 2Hospices Civils de Lyon-bioMérieux Research Unit on Rheumatoid Arthritis, Hopital Edouard Herriot, Lyon, France
  3. 3Service de Biostatistiques HCL, Laboratoire de Biostatistique-Santé, Université Claude Bernard Lyon 1, Lyon, France
  1. Correspondence to:
    Professor P Miossec
    Clinical Immunology Unit, Departments of Immunology and Rheumatology, Hôpital Edouard Hérriot, 69437 Lyon Cedex 03, France; miossec{at}univ-lyon1.fr

Abstract

Objective: To investigate whether ethnic differences exist in the effect of the shared epitope and selected cytokine gene polymorphisms on the susceptibility and severity of rheumatoid arthritis in Syria (Damascus) and France (Rhône-Alpes area).

Methods: 156 patients with rheumatoid arthritis and 120 healthy controls from Syria were compared with 512 patients with rheumatoid arthritis and 471 healthy controls from France. Shared epitope status, cytokine gene polymorphisms interleukin (IL)-1B +3954, IL-1RN +2018 and tumour necrosis factor α promoter (−238 and −308) were analysed by enzyme-linked oligosorbent assay. Joint destruction was defined by a right wrist Larsen score ⩾2. Odds ratios (ORs) were calculated.

Results: In both countries, a dose effect was observed between the shared epitope copy number and rheumatoid arthritis (Syria: OR 1 v 0 copies = 1.6, p = NS; OR 2 v 0 = 15.3, p<0.01; and France: OR 1 v 0 = 2.3, p<0.001; OR 2 v 0 = 7.2, p<0.001). A dose effect was also observed between the shared epitope copy number and joint destruction in Syria (OR 1 v 0 = 2.2, p = NS; OR 2 v 0 = 9.9, p<0.01) and France (OR 1 v 0 = 1.8, p<0.01; OR 2 v 0 = 4.8, p = 0.001). The dose effect of the shared epitope was greater in Syria than in France. Only the −238 tumour necrosis factor α polymorphism was associated with joint destruction in the Syrian population (p<0.05). However, after adjustment for age, sex, disease duration and rheumatoid factor for severity, this association disappeared.

Conclusion: The frequency of the shared epitope was increased in the French population with rheumatoid arthritis and in controls, but the association between the shared epitope and joint destruction was more pronounced in the Syrian population, with an OR of almost 10 for the homozygotes.

  • HLA, human leucocyte antigen
  • IL, interleukin
  • PCR, polymerase chain reaction
  • SNP, single-nucleotide polymorphism
  • TNF, tumour necrosis factor

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Footnotes

  • Published Online First 20 October 2006

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