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IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis

Citation

Metwally, M and Thabet, K and Bayoumi, A and Nikpour, M and Stevens, W and Sahhar, J and Zochling, J and Roddy, J and Tymms, K and Strickland, G and Lester, S and Rischmueller, M and Ngian, GS and Walker, J and Hissaria, P and Shaker, O and Liddle, C and Manolios, N and Beretta, L and Proudman, S and George, J and Eslam, M, IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis, Scientific Reports, 9, (1) Article 14834. ISSN 2045-2322 (2019) [Refereed Article]


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Copyright Statement

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI: doi:10.1038/s41598-019-50709-9

Abstract

Fibrosis across different organs and tissues is likely to share common pathophysiological mechanisms and pathways. Recently, a polymorphism (rs12979860) near the interferon lambda gene (IFNL3) was shown to be associated with fibrosis in liver across multiple disease etiologies. We determined whether this variant is a risk factor for pulmonary fibrosis (PF) and worsening cutaneous fibrosis in systemic sclerosis (SSc). Caucasian patients with SSc (n = 733) were genotyped to test for association with the presence of PF and worsening of skin fibrosis. Serum IFN-λ3 levels from 200 SSc cases were evaluated. An association of the IFNL3 polymorphism with PF was demonstrated (OR: 1.66 (95% CI: 1.142-2.416, p = 0.008). The IFNL3 variant was not a risk factor for worsening of skin fibrosis. Functionally, IFN-λ3 serum levels were higher among subjects with PF compared to those unaffected (P < 0.0001). In conclusion, IFNL3 serum levels and the genetic variant known to be associated with liver fibrosis are similarly linked to PF, but not to worsening of skin fibrosis in SSc. These data highlight both common fibrosis pathways operating between organs, as well as differential effects within the same disease.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Rheumatology and arthritis
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Zochling, J (Dr Jane Zochling)
ID Code:138050
Year Published:2019
Web of Science® Times Cited:10
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-03-22
Last Modified:2020-04-03
Downloads:10 View Download Statistics

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