IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

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IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis. / Eslam, Mohammed; McLeod, Duncan; Kelaeng, Kebitsaone Simon; Mangia, Alessandra; Berg, Thomas; Thabet, Khaled; Irving, William L; Dore, Gregory J; Sheridan, David; Grønbæk, Henning; Abate, Maria Lorena; Hartmann, Rune; Bugianesi, Elisabetta; Spengler, Ulrich; Rojas, Angela; Booth, David R.; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Mahajan, Hema; Fischer, Janett; Nattermann, Jacob; Douglas, Mark W; Liddle, Christopher; Powell, Elizabeth; Romero-Gomez, Manuel; George, Jacob; Int Liver Dis Genetics Consortium.

In: Nature Genetics, Vol. 49, No. 5, 05.2017, p. 795-800.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperLetterResearchpeer-review

Harvard

Eslam, M, McLeod, D, Kelaeng, KS, Mangia, A, Berg, T, Thabet, K, Irving, WL, Dore, GJ, Sheridan, D, Grønbæk, H, Abate, ML, Hartmann, R, Bugianesi, E, Spengler, U, Rojas, A, Booth, DR, Weltman, M, Mollison, L, Cheng, W, Riordan, S, Mahajan, H, Fischer, J, Nattermann, J, Douglas, MW, Liddle, C, Powell, E, Romero-Gomez, M, George, J & Int Liver Dis Genetics Consortium 2017, 'IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis', Nature Genetics, vol. 49, no. 5, pp. 795-800. https://doi.org/10.1038/ng.3836

APA

Eslam, M., McLeod, D., Kelaeng, K. S., Mangia, A., Berg, T., Thabet, K., Irving, W. L., Dore, G. J., Sheridan, D., Grønbæk, H., Abate, M. L., Hartmann, R., Bugianesi, E., Spengler, U., Rojas, A., Booth, D. R., Weltman, M., Mollison, L., Cheng, W., ... Int Liver Dis Genetics Consortium (2017). IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis. Nature Genetics, 49(5), 795-800. https://doi.org/10.1038/ng.3836

CBE

Eslam M, McLeod D, Kelaeng KS, Mangia A, Berg T, Thabet K, Irving WL, Dore GJ, Sheridan D, Grønbæk H, Abate ML, Hartmann R, Bugianesi E, Spengler U, Rojas A, Booth DR, Weltman M, Mollison L, Cheng W, Riordan S, Mahajan H, Fischer J, Nattermann J, Douglas MW, Liddle C, Powell E, Romero-Gomez M, George J, Int Liver Dis Genetics Consortium. 2017. IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis. Nature Genetics. 49(5):795-800. https://doi.org/10.1038/ng.3836

MLA

Vancouver

Eslam M, McLeod D, Kelaeng KS, Mangia A, Berg T, Thabet K et al. IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis. Nature Genetics. 2017 May;49(5):795-800. https://doi.org/10.1038/ng.3836

Author

Eslam, Mohammed ; McLeod, Duncan ; Kelaeng, Kebitsaone Simon ; Mangia, Alessandra ; Berg, Thomas ; Thabet, Khaled ; Irving, William L ; Dore, Gregory J ; Sheridan, David ; Grønbæk, Henning ; Abate, Maria Lorena ; Hartmann, Rune ; Bugianesi, Elisabetta ; Spengler, Ulrich ; Rojas, Angela ; Booth, David R. ; Weltman, Martin ; Mollison, Lindsay ; Cheng, Wendy ; Riordan, Stephen ; Mahajan, Hema ; Fischer, Janett ; Nattermann, Jacob ; Douglas, Mark W ; Liddle, Christopher ; Powell, Elizabeth ; Romero-Gomez, Manuel ; George, Jacob ; Int Liver Dis Genetics Consortium. / IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis. In: Nature Genetics. 2017 ; Vol. 49, No. 5. pp. 795-800.

Bibtex

@article{60c6bf77720c431293243c3c3275dde1,
title = "IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis",
abstract = "Genetic variation in the IFNL3-IFNL4 (interferon-lambda 3-interferon-lambda 4) region is associated with hepatic inflammation and fibrosis1-4. Whether IFN-lambda 3 or IFN-lambda 4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-lambda 3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-lambda 4, but produces IFN-lambda 3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-lambda 4 protein and reduces IFN-lambda 4 activity, or between patients encoding functionally defective IFN-lambda 4 (IFN-lambda 4-Ser70) and those encoding fully active IFN-lambda 4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) 5,6 were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-lambda 3 rather than IFN-lambda 4 likely mediates IFNL3-IFNL4 haplotypedependent hepatic inflammation and fibrosis.",
keywords = "GENOME-WIDE-ASSOCIATION, INTERFERON-STIMULATED GENES, C VIRUS, LIVER FIBROSIS, HCV CLEARANCE, III INTERFERONS, SOLID-ORGAN, IL28B GENE, LAMBDA 4, INFECTION",
author = "Mohammed Eslam and Duncan McLeod and Kelaeng, {Kebitsaone Simon} and Alessandra Mangia and Thomas Berg and Khaled Thabet and Irving, {William L} and Dore, {Gregory J} and David Sheridan and Henning Gr{\o}nb{\ae}k and Abate, {Maria Lorena} and Rune Hartmann and Elisabetta Bugianesi and Ulrich Spengler and Angela Rojas and Booth, {David R.} and Martin Weltman and Lindsay Mollison and Wendy Cheng and Stephen Riordan and Hema Mahajan and Janett Fischer and Jacob Nattermann and Douglas, {Mark W} and Christopher Liddle and Elizabeth Powell and Manuel Romero-Gomez and Jacob George and {Int Liver Dis Genetics Consortium}",
year = "2017",
month = may,
doi = "10.1038/ng.3836",
language = "English",
volume = "49",
pages = "795--800",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",

}

RIS

TY - JOUR

T1 - IFN-lambda 3, not IFN-lambda 4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis

AU - Eslam, Mohammed

AU - McLeod, Duncan

AU - Kelaeng, Kebitsaone Simon

AU - Mangia, Alessandra

AU - Berg, Thomas

AU - Thabet, Khaled

AU - Irving, William L

AU - Dore, Gregory J

AU - Sheridan, David

AU - Grønbæk, Henning

AU - Abate, Maria Lorena

AU - Hartmann, Rune

AU - Bugianesi, Elisabetta

AU - Spengler, Ulrich

AU - Rojas, Angela

AU - Booth, David R.

AU - Weltman, Martin

AU - Mollison, Lindsay

AU - Cheng, Wendy

AU - Riordan, Stephen

AU - Mahajan, Hema

AU - Fischer, Janett

AU - Nattermann, Jacob

AU - Douglas, Mark W

AU - Liddle, Christopher

AU - Powell, Elizabeth

AU - Romero-Gomez, Manuel

AU - George, Jacob

AU - Int Liver Dis Genetics Consortium

PY - 2017/5

Y1 - 2017/5

N2 - Genetic variation in the IFNL3-IFNL4 (interferon-lambda 3-interferon-lambda 4) region is associated with hepatic inflammation and fibrosis1-4. Whether IFN-lambda 3 or IFN-lambda 4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-lambda 3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-lambda 4, but produces IFN-lambda 3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-lambda 4 protein and reduces IFN-lambda 4 activity, or between patients encoding functionally defective IFN-lambda 4 (IFN-lambda 4-Ser70) and those encoding fully active IFN-lambda 4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) 5,6 were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-lambda 3 rather than IFN-lambda 4 likely mediates IFNL3-IFNL4 haplotypedependent hepatic inflammation and fibrosis.

AB - Genetic variation in the IFNL3-IFNL4 (interferon-lambda 3-interferon-lambda 4) region is associated with hepatic inflammation and fibrosis1-4. Whether IFN-lambda 3 or IFN-lambda 4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-lambda 3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-lambda 4, but produces IFN-lambda 3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-lambda 4 protein and reduces IFN-lambda 4 activity, or between patients encoding functionally defective IFN-lambda 4 (IFN-lambda 4-Ser70) and those encoding fully active IFN-lambda 4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) 5,6 were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-lambda 3 rather than IFN-lambda 4 likely mediates IFNL3-IFNL4 haplotypedependent hepatic inflammation and fibrosis.

KW - GENOME-WIDE-ASSOCIATION

KW - INTERFERON-STIMULATED GENES

KW - C VIRUS

KW - LIVER FIBROSIS

KW - HCV CLEARANCE

KW - III INTERFERONS

KW - SOLID-ORGAN

KW - IL28B GENE

KW - LAMBDA 4

KW - INFECTION

U2 - 10.1038/ng.3836

DO - 10.1038/ng.3836

M3 - Letter

C2 - 28394349

VL - 49

SP - 795

EP - 800

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -