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Rheumatoid arthritis and genetic markers in Syrian and French populations: different impact of the shared epitope
  1. Leyla Kazkaz
  1. Damascus hospital, France
    1. Hubert Marotte
    1. Edouard Herriot Hospital, France
      1. Mayssa Hamwi
      1. Edouard Herriot Hospital, France
        1. Marie Angélique Cazalis
        1. Edouard Herriot Hospital, France
          1. Pascal Roy
          1. Service de Biostatistiques HCL, France
            1. Bruno Mougin
            1. Edouard Herriot Hospital, France
              1. Pierre Miossec (miossec{at}univ-lyon1.fr)
              1. Edouard Herriot Hospital, France

                Abstract

                Objective: We investigated whether ethnic differences exist on the effect of the Shared Epitope (SE) and selected cytokine gene polymorphisms on the susceptibility and the severity of rheumatoid arthritis (RA) in Syria (Damascus) and France (Rhône-Alpes area).

                Methods: 156 RA patients and 120 healthy controls (HC) from Syria were compared with 512 RA patients and 471 HC from France. SE status and cytokine gene polymorphisms: IL-1B +3954, IL-1RN +2018 and TNFA promoter (-238 and -308) were analyzed by ELOSA. Joint destruction was defined by a right wrist Larsen score 2. Odds ratios (OR) were calculated.

                Results: In both countries, a dose effect was observed between the SE copy number and RA in Syria (OR 1 vs. 0 copy =1.6, p=NS; OR 2 vs. 0 =15.3, p<0.01) and France (OR 1 vs. 0 =2.3, p<0.001; OR 2 vs. 0 =7.2, p<0.001). A dose effect was also observed between the SE copy number and joint destruction in Syria (OR 1 vs. 0 =2.2, p=NS; OR 2 vs. 0 =9.9, p<0.01) and France (OR 1 vs. 0 =1.8, p<0.01; OR 2 vs. 0 =4.8, p=0.001). The dose effect of the SE was greater in Syria than in France. Only the -238 TNF polymorphism was associated with joint destruction in the Syrian population (p<0.05). However, after adjustment for age, sex, disease duration and RF for severity, this association disappeared.

                Conclusion: The frequency of the SE was increased in the French RA and control populations but the association between the SE and joint destruction was more pronounced in the Syrian population with an OR of almost 10 for the homozygotes.

                • cytokines
                • genetics
                • rheumatoid arthritis
                • shared epitope

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