Interferon-[lambda] rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease
Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of inte...
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Published in | Nature communications Vol. 6; p. 6422 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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London
Nature Publishing Group
01.03.2015
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Abstract | Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis. |
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AbstractList | Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis. |
Author | Cheng, Wendy Eslam, Mohammed Mcleod, Duncan Hashem, Ahmed M Shaker, Olfat Powell, Elizabeth Irving, William L Dore, Gregory J Chan, Henry Lk Liddle, Christopher Armstrong, Nicola J Spengler, Ulrich Mangia, Alessandra Douglas, Mark W Leung, Reynold Riordan, Stephen Sheridan, David Fischer, Janett Ahlenstiel, Golo Weltman, Martin Mollison, Lindsay Adams, Leon A Berg, Thomas Abate, Maria L Bugianesi, Elisabetta Romero-gomez, Manuel George, Jacob Nattermann, Jacob Booth, David R |
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Title | Interferon-[lambda] rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease |
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