Department of Rheumatology, DHU FIRE, Assistance Publique Hôpitaux de Paris, Bichat Hospital, Université Paris Diderot, PRES Sorbonne Paris Cité, Paris, France.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Ann Rheum Dis. 2014 Oct;73(10):1840-3. doi: 10.1136/annrheumdis-2014-205539. Epub 2014 Jun 16.
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.
我们最近报道了 SPP1 rs9138 和 rs11439060 功能变体与类风湿关节炎 (RA) 风险的关联，在抗瓜氨酸蛋白抗体 (ACPA) 阴性患者中这种关联更大。我们假设 SPP1 可能导致 RA 关节破坏的严重程度，特别是在 ACPA 阴性人群中。
ESPOIR 队列中的 RA 患者接受了 SPP1 rs9138 和 rs11439060 的基因分型。在首次就诊时以及 1 年和 2 年随访时获得了手部和足部的 X 光片。通过 ACPA 状态进行关联分析。对莱顿早期关节炎诊所 (EAC) 队列的相关亚组进行了重复研究。
在 ESPOIR 队列（652 例患者）中，rs9138 与 2 年时关节破坏的放射学进展显著相关，这种关联仅限于 358 例 ACPA 阴性患者（p=0.034）。在莱顿 EAC 队列的重复研究中（273 例 ACPA 阴性患者），与 rs9138 完全连锁不平衡的 rs4754 在 ACPA 阴性患者中与 2 年和 7 年随访时的关节损伤进展显著相关（p=0.019 和 p=0.005）。两个队列的综合分析显示，每个次要等位基因每年导致关节破坏的速率增加 0.95 倍（p=0.022）。
SPP1 rs9138 变体导致 ACPA 阴性 RA 患者的关节破坏进展。
