APHP, Hôpital Bichat, Service de Rhumatologie, DHU FIRE, Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Eur Respir J. 2017 May 11;49(5). doi: 10.1183/13993003.02314-2016. Print 2017 May.
Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the , , or coding regions The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of , , or mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10). Telomeres were shorter in RA-ILD patients with a , or mutation than in controls (p=2.87×10).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.
尽管类风湿关节炎相关间质性肺病（RA-ILD）的患病率和死亡率很高，但人们对其发病机制知之甚少。鉴于家族性肺纤维化（FPF）和 RA-ILD 常共享间质性肺炎的常见模式和常见环境危险因素，我们假设这两种疾病可能具有其他共同的危险因素，包括与 FPF 相关的基因。我们的目的是确定与 RA-ILD 相关的 FPF 风险基因的编码突变。
我们使用外显子组测序（WES），然后对离散数量的 FPF 相关基因进行受限分析，并进行负担测试，以评估与对照组相比，RA-ILD 患者的突变数量是否过多。
在纳入的 101 例 RA-ILD 患者中，有 12 例（11.9%）在 、 、 或 编码区域中发现了 13 个 WES 鉴定的杂合突变。基于 81 例 RA-ILD 患者和 1010 例欧洲血统对照，负担测试显示 RA-ILD 患者中 、 、 或 突变过多（OR 3.17，95%CI 1.53-6.12；p=9.45×10）。与对照组相比，携带 、 或 突变的 RA-ILD 患者的端粒较短（p=2.87×10）。
我们的结果支持 FPF 相关基因对 RA-ILD 易感性的贡献。
