RT Journal Article
SR Electronic
T1 Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1602314
DO 10.1183/13993003.02314-2016
VO 49
IS 5
A1 Pierre-Antoine Juge
A1 Raphaël Borie
A1 Caroline Kannengiesser
A1 Steven Gazal
A1 Patrick Revy
A1 Lidwine Wemeau-Stervinou
A1 Marie-Pierre Debray
A1 Sébastien Ottaviani
A1 Sylvain Marchand-Adam
A1 Nadia Nathan
A1 Gabriel Thabut
A1 Christophe Richez
A1 Hilario Nunes
A1 Isabelle Callebaut
A1 Aurélien Justet
A1 Nicolas Leulliot
A1 Amélie Bonnefond
A1 David Salgado
A1 Pascal Richette
A1 Jean-Pierre Desvignes
A1 Huguette Lioté
A1 Philippe Froguel
A1 Yannick Allanore
A1 Olivier Sand
A1 Claire Dromer
A1 René-Marc Flipo
A1 Annick Clément
A1 Christophe Béroud
A1 Jean Sibilia
A1 Baptiste Coustet
A1 Vincent Cottin
A1 Marie-Christophe Boissier
A1 Benoit Wallaert
A1 Thierry Schaeverbeke
A1 Florence Dastot le Moal
A1 Aline Frazier
A1 Christelle Ménard
A1 Martin Soubrier
A1 Nathalie Saidenberg
A1 Dominique Valeyre
A1 Serge Amselem
A1 the FREX consortium
A1 Catherine Boileau
A1 Bruno Crestani
A1 Philippe Dieudé
YR 2017
UL http://erj.ersjournals.com/content/49/5/1602314.abstract
AB 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.Contribution of TERT, RTEL1, PARN and SFTPC mutations to rheumatoid interstitial lung disease susceptibility http://ow.ly/SXEm30a98Ic