Pierre-Antoine Juge1, Hanna W van Steenbergen2, Arnaud Constantin3, Gabriel J Tobon4, Thierry Schaeverbeke5, Steven Gazal6, Bernard Combe7, Valérie Devauchelle-Pensec4, Delphine Nigon3, Annette H M van der Helm-van Mil2, Philippe Dieude8. 1. Department of Rheumatology, DHU FIRE, Assistance Publique Hôpitaux de Paris, Bichat Hospital, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France. 2. Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. 3. UMR 1027, INSERM, Toulouse III University and Department of Rheumatology, Purpan Hospital, CHU Toulouse, Toulouse, France. 4. Department of Rheumatology, Morvan Hospital, Cavale Blanche Hospital, Brittany University, Brest, France. 5. Department of Rheumatology, Pellegrin Hospital, Bordeaux Selagen University, Bordeaux, France. 6. Plateforme de Génomique Constitutionnelle Assistance Publique Hôpitaux de Paris, Bichat Hospital, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France. 7. Department of Rheumatology, Montpellier University Hospital, Montpellier, France. 8. Department of Rheumatology, DHU FIRE, Assistance Publique Hôpitaux de Paris, Bichat Hospital, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France INSERM U699, Bichat Faculty of Medicine, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
Abstract
OBJECTIVE: We recently reported an association of the SPP1 rs9138 and rs11439060 functional variants with the risk of rheumatoid arthritis (RA), the association being greater in anti-citrullinated protein autoantibody (ACPA)-negative patients. We hypothesised that SPP1 may contribute to the severity of joint destruction in RA, specifically in the ACPA-negative population. METHODS: Patients with RA in the ESPOIR cohort underwent genotyping for SPP1 rs9138 and rs11439060. Radiographs of the hands and feet were obtained at the first visit and at 1- and 2-year follow-up. Association analyses were performed by ACPA status. A replication study of the relevant subset of the Leiden Early Arthritis Clinic (EAC) cohort was performed. RESULTS: In the ESPOIR cohort (652 patients), rs9138 was significantly associated with radiological progression of joint destruction at 2 years, the association being restricted to 358 ACPA-negative patients (p=0.034). In the replication study with the Leiden EAC cohort (273 ACPA-negative patients), rs4754, which is in complete linkage disequilibrium with rs9138, was significantly associated with joint damage progression in ACPA-negative patients at 2- and 7-year follow-up (p=0.019 and p=0.005, respectively). Combined analysis of the two cohorts revealed a 0.95-fold rate of joint destruction per year per minor allele (p=0.022). CONCLUSIONS: The SPP1 rs9138 variant contributes to joint damage progression in ACPA-negative RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
OBJECTIVE: We recently reported an association of the SPP1rs9138 and rs11439060 functional variants with the risk of rheumatoid arthritis (RA), the association being greater in anti-citrullinated protein autoantibody (ACPA)-negative patients. We hypothesised that SPP1 may contribute to the severity of joint destruction in RA, specifically in the ACPA-negative population. METHODS:Patients with RA in the ESPOIR cohort underwent genotyping for SPP1rs9138 and rs11439060. Radiographs of the hands and feet were obtained at the first visit and at 1- and 2-year follow-up. Association analyses were performed by ACPA status. A replication study of the relevant subset of the Leiden Early Arthritis Clinic (EAC) cohort was performed. RESULTS: In the ESPOIR cohort (652 patients), rs9138 was significantly associated with radiological progression of joint destruction at 2 years, the association being restricted to 358 ACPA-negative patients (p=0.034). In the replication study with the Leiden EAC cohort (273 ACPA-negative patients), rs4754, which is in complete linkage disequilibrium with rs9138, was significantly associated with joint damage progression in ACPA-negative patients at 2- and 7-year follow-up (p=0.019 and p=0.005, respectively). Combined analysis of the two cohorts revealed a 0.95-fold rate of joint destruction per year per minor allele (p=0.022). CONCLUSIONS: The SPP1rs9138 variant contributes to joint damage progression in ACPA-negative RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Entities:
Keywords:
Ant-CCP; Autoantibodies; Early Rheumatoid Arthritis; Gene Polymorphism; Rheumatoid Arthritis
Authors: Sebastien Viatte; James C Lee; Bo Fu; Marion Espéli; Mark Lunt; Jack N E De Wolf; Lily Wheeler; John A Reynolds; Madhura Castelino; Deborah P M Symmons; Paul A Lyons; Anne Barton; Kenneth G C Smith Journal: Arthritis Rheumatol Date: 2016-11 Impact factor: 10.995
Authors: Pierre-Antoine Juge; Steven Gazal; Arnaud Constantin; Xavier Mariette; Bernard Combe; Jacques Tebib; Maxime Dougados; Jean Sibilia; Xavier Le Loet; Philippe Dieudé Journal: RMD Open Date: 2017-09-28