Journal
EUROPEAN RESPIRATORY JOURNAL
Volume 49, Issue 5, Pages -Publisher
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/13993003.02314-2016
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Funding
- Societe Francaise de Rhumatologie
- Club Rhumatismes Inflammation
- la Chancellerie des Universites de Paris (legs Poix)
- Sorbonne Paris Cite (FPI-SPC Program)
- Agence Nationale de la Recherche [ANR-10-LABX-46, ANR-10-EQPX-07-01, ANR-14-CE10-0006, ANR-10-INBS-09]
- France Genomique National Infrastructure
- Pfizer
- Roche
- Chugai
- Centre de Resources Biologiques Hopital Bichat, Paris, France
- Agence Nationale de la Recherche (ANR) [ANR-14-CE10-0006] Funding Source: Agence Nationale de la Recherche (ANR)
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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= 9.45x10(-4)). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p= 2.87x10(-2)). Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.
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