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

International Hepatitis C Genetics Consortium (IHCGC)

doi:10.1038/ncomms7422

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

International Hepatitis C Genetics Consortium (IHCGC)

Research output: Contribution to journal › Article › peer-review

155 Citations (Scopus)

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.

Original language	English
Article number	6422
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7422
Publication status	Published or Issued - Mar 2015
Externally published	Yes

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/ncomms7422

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@article{391804232cd44c859469bf27ca87976f,

title = "Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease",

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.",

author = "{International Hepatitis C Genetics Consortium (IHCGC)} and Mohammed Eslam and Hashem, {Ahmed M.} and Reynold Leung and Manuel Romero-Gomez and Thomas Berg and Dore, {Gregory J.} and Chan, {Henry L.K.} and Irving, {William L.} and David Sheridan and Abate, {Maria L.} and Adams, {Leon A.} and Alessandra Mangia and Martin Weltman and Elisabetta Bugianesi and Ulrich Spengler and Olfat Shaker and Janett Fischer and Lindsay Mollison and Wendy Cheng and Elizabeth Powell and Jacob Nattermann and Stephen Riordan and Duncan McLeod and Armstrong, {Nicola J.} and Douglas, {Mark W.} and Christopher Liddle and Booth, {David R.} and Jacob George and Golo Ahlenstiel and Javier Ampuero and Margaret Bassendine and Wong, {Vincent W.S.} and Chiara Rosso and Rose White and Lavinia Mezzabotta and Vijayaprakash Suppiah and Monika Michalk and Barbara Malik and Gail Matthews and Tanya Applegate and Jason Grebely and Vincenzo Fragomeli and Jonsson, {Julie R.} and Rosanna Santaro",

year = "2015",

month = mar,

doi = "10.1038/ncomms7422",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

AU - International Hepatitis C Genetics Consortium (IHCGC)

AU - Eslam, Mohammed

AU - Hashem, Ahmed M.

AU - Leung, Reynold

AU - Romero-Gomez, Manuel

AU - Berg, Thomas

AU - Dore, Gregory J.

AU - Chan, Henry L.K.

AU - Irving, William L.

AU - Sheridan, David

AU - Abate, Maria L.

AU - Adams, Leon A.

AU - Mangia, Alessandra

AU - Weltman, Martin

AU - Bugianesi, Elisabetta

AU - Spengler, Ulrich

AU - Shaker, Olfat

AU - Fischer, Janett

AU - Mollison, Lindsay

AU - Cheng, Wendy

AU - Powell, Elizabeth

AU - Nattermann, Jacob

AU - Riordan, Stephen

AU - McLeod, Duncan

AU - Armstrong, Nicola J.

AU - Douglas, Mark W.

AU - Liddle, Christopher

AU - Booth, David R.

AU - George, Jacob

AU - Ahlenstiel, Golo

AU - Ampuero, Javier

AU - Bassendine, Margaret

AU - Wong, Vincent W.S.

AU - Rosso, Chiara

AU - White, Rose

AU - Mezzabotta, Lavinia

AU - Suppiah, Vijayaprakash

AU - Michalk, Monika

AU - Malik, Barbara

AU - Matthews, Gail

AU - Applegate, Tanya

AU - Grebely, Jason

AU - Fragomeli, Vincenzo

AU - Jonsson, Julie R.

AU - Santaro, Rosanna

PY - 2015/3

Y1 - 2015/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84924362729&partnerID=8YFLogxK

U2 - 10.1038/ncomms7422

DO - 10.1038/ncomms7422

M3 - Article

C2 - 25740255

AN - SCOPUS:84924362729

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6422

ER -

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

Abstract

ASJC Scopus subject areas

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