Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis
- 1 May 2017
- journal article
- research article
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 49 (5), 1602314
- https://doi.org/10.1183/13993003.02314-2016
Abstract
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 TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53–6.12; p=9.45×10−4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10−2). Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.Keywords
Funding Information
- Sorbonne Paris Cité
- Chancellerie des Universités de Paris
- Société Française de Rhûmatologie
- Pfizer
- Agence Nationale de la Recherche (ANR-10-LABX-46, ANR-10-EQPX-07-01, ANR-14-CE10-000)
- Centre de Resources Biologiques Hôpital Bichat
- Chugai Pharmaceutical
- Roche
- Club Rhumatismes Inflammation
- France Génomique
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