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

Mayada Metwally, Khaled Thabet, Ali Bayoumi, Mandana Nikpour, Wendy Stevens, Joanne Sahhar, Jane Zochling, Janet Roddy, Kathleen Tymms, Gemma Strickland, Susan Lester, Maureen Rischmueller, Gene Siew Ngian, Jennifer Walker, Pravin Hissaria, Olfat Shaker, Christopher Liddle, Nicholas Manolios, Lorenzo Beretta, Susanna ProudmanJacob George, Mohammed Eslam

    Research output: Contribution to journalArticlepeer-review

    5 Citations (Scopus)

    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.

    Original languageEnglish
    Article number14834
    Number of pages5
    JournalScientific Reports
    Volume9
    DOIs
    Publication statusPublished - 16 Oct 2019

    Bibliographical note

    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 Cre-ative 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. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

    Keywords

    • Genetics research
    • Translational research
    • Pulmonary fibrosis
    • Systemic sclerosis

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