SPP1 rs9138 variant contributes to the severity of radiological damage in anti-citrullinated protein autoantibody-negative rheumatoid arthritis.

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Juge, Pierre-Antoine | van Steenbergen, Hanna W | Constantin, Arnaud | Tobon, Gabriel J | Schaeverbeke, Thierry | Gazal, Steven | Combe, Bernard | Devauchelle-Pensec, Valérie | Nigon, Delphine | van Der Helm-van Mil, Annette H M | Dieude, Philippe

Edité par CCSD ; BMJ Publishing Group -

International audience. 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. . 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. . 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). . The SPP1 rs9138 variant contributes to joint damage progression in ACPA-negative RA.

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