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.

Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

ABATE, Maria Lorena;BUGIANESI, Elisabetta;ROSSO, CHIARA;MEZZABOTTA, Lavinia;
2015

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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Cohort Studies; Female; Genotype; Hepatitis, Chronic; Humans; Interleukins; Liver; Liver Cirrhosis; Logistic Models; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Sex Factors; Statistics, Nonparametric; Biochemistry, Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)
Eslam, Mohammed; Hashem, Ahmed M.; Leung, Reynold; Romero-Gomez, Manuel; Berg, Thomas; Dore, Gregory J.; Chan, Henry L.K.; Irving, William L.; Sheridan, David; Abate, Maria L.; Adams, Leon A.; Mangia, Alessandra; Weltman, Martin; Bugianesi, Elisabetta; Spengler, Ulrich; Shaker, Olfat; Fischer, Janett; Mollison, Lindsay; Cheng, Wendy; Powell, Elizabeth; Nattermann, Jacob; Riordan, Stephen; Mcleod, Duncan; Armstrong, Nicola J.; Douglas, Mark W.; Liddle, Christopher; Booth, David R.; George, Jacob; Ahlenstiel, Golo; Ampuero, Javier; Bassendine, Margaret; Wong, Vincent W S; Rosso, Chiara; White, Rose; Mezzabotta, Lavinia; Suppiah, Vijayaprakash; Michalk, Monika; Malik, Barbara; Matthews, Gail; Applegate, Tanya; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R; Santaro, Rosanna
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1561132
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