138050 - IFNL3 genotype is associated with pulmonary fibrosis.pdf (882.83 kB)
IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis
journal contributionposted on 2023-05-20, 11:57 authored by Metwally, M, Thabet, K, Bayoumi, A, Nikpour, M, Stevens, W, Sahhar, J, Zochling, J, Roddy, J, Tymms, K, Strickland, G, Lester, S, Rischmueller, M, Ngian, GS, Walker, J, Hissaria, P, Shaker, O, Liddle, C, Manolios, N, Beretta, L, Proudman, S, George, J, Eslam, M
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.
Publication titleScientific Reports
Department/SchoolMenzies Institute for Medical Research
PublisherNature Publishing Group
Place of publicationUnited Kingdom
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