Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis
European Respiratory Journal, 2017•Eur Respiratory Soc
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 …
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 …
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.
European Respiratory Society