Familial pulmonary fibrosis-linked genes may contribute to RA-ILD susceptibility

16 May, 2017

Researchers have identified for the first time shared genetic risk factors between the rheumatoid arthritis-associated interstitial lung disease (RA-ILD) phenotype and familial pulmonary fibrosis (FPF).

The findings, published in the European Respiratory Journal, suggest that the presence of FPF-linked genes contributes to an increased susceptibility to RA-ILD.

Using a cohort of 101 RA-ILD patients, researchers carried out whole exome sequencing (WES) followed by restricted analysis of nine genes linked to familial pulmonary fibrosis (FPF), to identify coding mutations of FPF-risk genes associated with RA-ILD. A burden test was also performed to assess the excess number of mutations in RA-ILD patients compared to 1010 controls of European ancestry.

WES identified relevant mutations in the TERT, RTEL1, PARN or SFTPC coding regions of nearly 12% of all RA-ILD patients. A burden analysis of 81 RA-ILD patients and controls of European ancestry revealed that RA-ILD patients had a significantly higher number of risk mutation than control subjects.

Patients with mutations in the TERT, RTEL1 or PARN genes were also found to have short telomeres in their peripheral blood leukocytes, suggesting that the mutations are biologically relevant.

The authors believe that the research demonstrates the value of WES combined with restricted candidate gene analysis in identifying RA-ILD-associated mutations, but note that due to the small number of patients within the cohort, the study design is not sufficient or appropriate for gene discovery.

Dr Paul J. Wolters discusses the new research in the context of existing knowledge of genetic risk factors in ILD in an accompanying editorial also published in the ERJ.

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