Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts) |
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| Institution: | 1. INSERM, UMR1027, 31062 Toulouse cedex 9, France;2. Université de Toulouse III, UMR1027, 31062 Toulouse cedex 9, France;3. Rheumatology Center, Purpan Teaching Hospital, CHU Toulouse, 1 place du Dr-Baylac, 31059 Toulouse cedex 9, France;4. Rheumatology Department, Lapeyronie Teaching Hospital, 34295 Montpellier cedex 5, France;5. Rheumatology Department, Claude Bernard-Bichat Teaching Hospital, Paris VII University, 75890 Paris cedex 18, France;6. Rheumatology Department, Hautepierre Teaching Hospital, 67098 Strasbourg cedex, France;7. Inserm UMR 1043, CPTP Toulouse Purpan, BP 3028, 31024 Toulouse cedex 3, France;8. Paris VII University, 75890 Paris cedex 18, France;9. INSERM U699, 75890 Paris cedex 18, France;1. Service de dermatologie, Centre Hospitalo-Universitaire de Strasbourg, Clinique dermatologique, 67098 Strasbourg cedex, France;2. Service de rhumatologie, centre de référence des maladies auto-immunes rares, Centre Hospitalo-Universitaire de Strasbourg, hôpital de Hautepierre, 1, avenue Molière, 67098 Strasbourg cedex, France;3. Service d’immunologie, Centre Hospitalo-Universitaire de Strasbourg, hôpital de Hautepierre, Nouvel hôpital civil, 67098 Strasbourg cedex, France;4. Service de physiologie et d’explorations fonctionnelles, Centre Hospitalo-Universitaire de Strasbourg, Nouvel hôpital civil, 67098 Strasbourg cedex, France;1. Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic;2. Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic;1. Pediatrics Center of Excellence, Children''s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;2. Research Center for Immunodeficiencies, Children''s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;3. Division of Immunology, Boston Children''s Hospital, Harvard Medical School, Boston, MA, USA;4. Molecular Immunology Research Center, and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;5. Universal Scientific Education and Research Network (USERN), Tehran, Iran;1. Service de rhumatologie I, Aix Marseille université, hôpital Sainte-Marguerite, AP–HM, 13009 Marseille, France;2. Service de médecine interne, HIA Ste-Anne, 83000 Toulon, France;3. Service d’anatomopathologie, HIA Laveran, 13013 Marseille, France;1. Division of Rheumatology, Department of Medicine DIMED, University of Padua, Via Giustiniani 2, 35128 Padua, Italy;2. Cardiology Clinic, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy |
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| Abstract: | ObjectivesTo assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.MethodsThis work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.ResultsThe AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR95%CI] = 1.921.14–3.22], p = 0.01) and in ACPA positive patients (OR95%CI] = 3.341.68–6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.031.94–18.69], p = 0.002) on the risk of erosions in ACPA+ patients.ConclusionA haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA. |
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| Keywords: | Rheumatoid arthritis IL-2RA IL-2RB Single nucleotid polymorphism Autoantibodies Disease progression |
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