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Associations between genetic factors, tobacco smoking and autoantibodies in familial and sporadic rheumatoid arthritis
  1. Laëtitia Michou (laetitiami{at}wanadoo.fr)
  1. GenHotel-EA3886, Evry-Genopole, France
    1. Vitor Hugo Teixeira (vitor8hugo{at}yahoo.com)
    1. GenHotel-EA3886, Evry-Genopole, France
      1. Céline Pierlot (pierlot{at}polyarthrite.net)
      1. GenHotel-EA3886, Evry-Genopole, France
        1. Sandra Lasbleiz (sandra.lasbleiz{at}lrb.aphp.fr)
        1. GenHotel-EA3886, Evry-Genopole, France
          1. Thomas Bardin (thomas.bardin{at}lrb.aphp.fr)
          1. GenHotel-EA3886, Evry-Genopole, France
            1. Philippe Dieudé (philippe.dieude{at}bch.aphp.fr)
            1. GenHotel-EA3886, Evry-Genopole, France
              1. Bernard Prum (prum{at}genopole.cnrs.fr)
              1. Laboratoire statistiques et génome, Evry, France
                1. François Cornélis (francois.cornelis{at}lrb.aphp.fr)
                1. GenHotel-EA3886, Evry-Genopole, France
                  1. Elisabeth Petit-Teixeira (epetit{at}polyarthrite.net)
                  1. GenHotel-EA3886, Evry-Genopole, France

                    Abstract

                    Objectives: The objective of this study was to investigate the association between genes (HLA-DRB1 and PTPN22) and tobacco smoking, separately as well as combined, and serological markers of rheumatoid arthritis (RA) in a French population of RA.

                    Methods: 274 RA patients with half of them belonging to RA multicase families, were genotyped for HLA-DRB1 allele and for PTPN22-1858 polymorphism. IgM rheumatoid factor and anti-CCP antibodies were determined by ELISA method. The search for association relied on Chi-square test and odds ratio with 95% confidence interval calculation. The interaction study relied on the departure-from-additivity-based method.

                    Results: The presence of at least one SE allele was associated with anti-CCP antibodies presence (82.5% versus 68.4%, P=0.02), particularly with HLA-DRB1*0401 allele (28.0% versus 16.4%, P=0.01). Tobacco exposure was associated with anti-CCP antibodies, but only in presence of SE. A tendency toward an interaction was found between tobacco, the presence of at least one HLA-DRB1*0401 allele and anti-CCP antibodies (attributable proportion due to interaction= +0.24 [-0.21 +0.76]). The cumulative dose of cigarettes smoking was correlated with anti-CCP antibodies titers (r=0.19, P=0.04). The presence of both SE and 1858T alleles was associated with a higher, but not significantly different, risk for anti-CCP antibodies presence than for each separately. No association was found between PTPN22-1858T allele and tobacco smoking for autoantibodies positivity.

                    Conclusion: Our findings suggest an association between SE alleles and tobacco smoking for anti-CCP positivity and a tendency toward an interaction between the HLA-DRB1*0401 allele and smoking for anti-CCP positivity in this sample of RA.

                    • PTPN22
                    • anti-CCP antibodies
                    • rheumatoid arthritis
                    • shared epitope
                    • tobacco smoking

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