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

Article scientifique 2019 Anglais

Résumé

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.

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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, G., Walker, J., Hissaria, P., Shaker, O., Liddle, C., Manolios, N., Beretta, L., Proudman, S., George, J., Eslam, M. (2019). IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis. https://doi.org/10.1038/s41598-019-50709-9

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Auteur(s)

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 Proudman Jacob George Mohammed Eslam

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