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Recently, a polymorphism (rs12979860) near the interferon lambda gene (<jats:italic>IFNL3<\/jats:italic>) 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\u2009=\u2009733) were genotyped to test for association with the presence of PF and worsening of skin fibrosis. Serum IFN-\u03bb3 levels from 200 SSc cases were evaluated. An association of the <jats:italic>IFNL3<\/jats:italic> polymorphism with PF was demonstrated (OR: 1.66 (95% CI: 1.142\u20132.416, p\u2009=\u20090.008). The <jats:italic>IFNL3<\/jats:italic> variant was not a risk factor for worsening of skin fibrosis. Functionally, IFN-\u03bb3 serum levels were higher among subjects with PF compared to those unaffected (P\u2009&lt;\u20090.0001). 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.<\/jats:p>","DOI":"10.1038\/s41598-019-50709-9","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T10:39:19Z","timestamp":1571222359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis"],"prefix":"10.1038","volume":"9","author":[{"given":"Mayada","family":"Metwally","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled","family":"Thabet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Bayoumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandana","family":"Nikpour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Sahhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Zochling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Roddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Tymms","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Strickland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Lester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Rischmueller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gene-Siew","family":"Ngian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pravin","family":"Hissaria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-3599","authenticated-orcid":false,"given":"Olfat","family":"Shaker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-6790","authenticated-orcid":false,"given":"Christopher","family":"Liddle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Manolios","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Beretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Proudman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-5476","authenticated-orcid":false,"given":"Jacob","family":"George","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Eslam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,16]]},"reference":[{"key":"50709_CR1","doi-asserted-by":"publisher","first-page":"167sr1","DOI":"10.1126\/scitranslmed.3004700","volume":"5","author":"SL Friedman","year":"2013","unstructured":"Friedman, S. 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