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

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 wheth...

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Veröffentlicht in:	Scientific reports 2019-10, Vol.9 (1), p.14834-5, Article 14834
Hauptverfasser:	Metwally, Mayada, Thabet, Khaled, Bayoumi, Ali, Nikpour, Mandana, Stevens, Wendy, Sahhar, Joanne, Zochling, Jane, Roddy, Janet, Tymms, Kathleen, Strickland, Gemma, Lester, Susan, Rischmueller, Maureen, Ngian, Gene-Siew, Walker, Jennifer, Hissaria, Pravin, Shaker, Olfat, Liddle, Christopher, Manolios, Nicholas, Beretta, Lorenzo, Proudman, Susanna, George, Jacob, Eslam, Mohammed
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Sprache:	eng
Schlagworte:	42/41 45/22 45/90 64/60 692/308/2056 692/308/575 Aged Female Fibrosis Gene polymorphism Genetic diversity Genetic Predisposition to Disease Genetic variance Humanities and Social Sciences Humans Interferon Interferons - blood Interferons - genetics Liver Cirrhosis - genetics Liver Cirrhosis - metabolism Liver diseases Lung diseases Male Middle Aged multidisciplinary Polymorphism Polymorphism, Single Nucleotide Pulmonary fibrosis Pulmonary Fibrosis - genetics Pulmonary Fibrosis - metabolism Risk factors Science Science (multidisciplinary) Scleroderma Scleroderma, Systemic - genetics Scleroderma, Systemic - metabolism Serum levels Skin Skin - pathology Systemic sclerosis
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creator	Metwally, Mayada Thabet, Khaled Bayoumi, Ali Nikpour, Mandana Stevens, Wendy Sahhar, Joanne Zochling, Jane Roddy, Janet Tymms, Kathleen Strickland, Gemma Lester, Susan Rischmueller, Maureen Ngian, Gene-Siew Walker, Jennifer Hissaria, Pravin Shaker, Olfat Liddle, Christopher Manolios, Nicholas Beretta, Lorenzo Proudman, Susanna George, Jacob Eslam, Mohammed
description	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
doi_str_mv	10.1038/s41598-019-50709-9
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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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Metwally, Mayada</au><au>Thabet, Khaled</au><au>Bayoumi, Ali</au><au>Nikpour, Mandana</au><au>Stevens, Wendy</au><au>Sahhar, Joanne</au><au>Zochling, Jane</au><au>Roddy, Janet</au><au>Tymms, Kathleen</au><au>Strickland, Gemma</au><au>Lester, Susan</au><au>Rischmueller, Maureen</au><au>Ngian, Gene-Siew</au><au>Walker, Jennifer</au><au>Hissaria, Pravin</au><au>Shaker, Olfat</au><au>Liddle, Christopher</au><au>Manolios, Nicholas</au><au>Beretta, Lorenzo</au><au>Proudman, Susanna</au><au>George, Jacob</au><au>Eslam, Mohammed</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-10-16</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>14834</spage><epage>5</epage><pages>14834-5</pages><artnum>14834</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><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. 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subjects	42/41 45/22 45/90 64/60 692/308/2056 692/308/575 Aged Female Fibrosis Gene polymorphism Genetic diversity Genetic Predisposition to Disease Genetic variance Humanities and Social Sciences Humans Interferon Interferons - blood Interferons - genetics Liver Cirrhosis - genetics Liver Cirrhosis - metabolism Liver diseases Lung diseases Male Middle Aged multidisciplinary Polymorphism Polymorphism, Single Nucleotide Pulmonary fibrosis Pulmonary Fibrosis - genetics Pulmonary Fibrosis - metabolism Risk factors Science Science (multidisciplinary) Scleroderma Scleroderma, Systemic - genetics Scleroderma, Systemic - metabolism Serum levels Skin Skin - pathology Systemic sclerosis
title	IFNL3 genotype is associated with pulmonary fibrosis in patients with systemic sclerosis
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