IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

Vijayaprakash Suppiah; Max Moldovan; Golo Ahlenstiel; Thomas Berg; Martin Weltman; Maria Lorena Abate; Margaret Bassendine; Ulrich Spengler; Gregory J. Dore; Elizabeth Powell; Stephen Riordan; David Sheridan; Antonina Smedile; Vincenzo Fragomeli; Tobias Müller; Melanie Bahlo; Graeme J. Stewart; David R. Booth; Jacob George

doi:10.1038/ng.447

IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

Vijayaprakash Suppiah, Max Moldovan, Golo Ahlenstiel, Thomas Berg, Martin Weltman, Maria Lorena Abate, Margaret Bassendine, Ulrich Spengler, Gregory J. Dore, Elizabeth Powell, Stephen Riordan, David Sheridan, Antonina Smedile, Vincenzo Fragomeli, Tobias Müller, Melanie Bahlo, Graeme J. Stewart, David R. Booth, Jacob George^*

^*Corresponding author for this work

Peninsula Medical School

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

Abstract

Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.

Original language	English
Pages (from-to)	1100-1104
Number of pages	0
Journal	Nat Genet
Volume	41
Issue number	10
DOIs	https://doi.org/10.1038/ng.447
Publication status	Published - Oct 2009

Keywords

Adult
Antiviral Agents
Australia
Drug Therapy
Combination
Female
Gene Expression Regulation
Genome-Wide Association Study
Genotype
Hepatitis C
Chronic
Humans
Interferon-alpha
Interferons
Interleukins
Male
Middle Aged
Polyethylene Glycols
Polymorphism
Single Nucleotide
Ribavirin
Treatment Outcome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.447

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Suppiah, V., Moldovan, M., Ahlenstiel, G., Berg, T., Weltman, M., Abate, M. L., Bassendine, M., Spengler, U., Dore, G. J., Powell, E., Riordan, S., Sheridan, D., Smedile, A., Fragomeli, V., Müller, T., Bahlo, M., Stewart, G. J., Booth, D. R., & George, J. (2009). IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet, 41(10), 1100-1104. https://doi.org/10.1038/ng.447

@article{1711ab7627f641efbfd55671656668d3,

title = "IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.",

abstract = "Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.",

keywords = "Adult, Antiviral Agents, Australia, Drug Therapy, Combination, Female, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Hepatitis C, Chronic, Humans, Interferon-alpha, Interferons, Interleukins, Male, Middle Aged, Polyethylene Glycols, Polymorphism, Single Nucleotide, Ribavirin, Treatment Outcome",

author = "Vijayaprakash Suppiah and Max Moldovan and Golo Ahlenstiel and Thomas Berg and Martin Weltman and Abate, {Maria Lorena} and Margaret Bassendine and Ulrich Spengler and Dore, {Gregory J.} and Elizabeth Powell and Stephen Riordan and David Sheridan and Antonina Smedile and Vincenzo Fragomeli and Tobias M{\"u}ller and Melanie Bahlo and Stewart, {Graeme J.} and Booth, {David R.} and Jacob George",

year = "2009",

month = oct,

doi = "10.1038/ng.447",

language = "English",

volume = "41",

pages = "1100--1104",

journal = "Nat Genet",

issn = "1546-1718",

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Suppiah, V, Moldovan, M, Ahlenstiel, G, Berg, T, Weltman, M, Abate, ML, Bassendine, M, Spengler, U, Dore, GJ, Powell, E, Riordan, S, Sheridan, D, Smedile, A, Fragomeli, V, Müller, T, Bahlo, M, Stewart, GJ, Booth, DR & George, J 2009, 'IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.', Nat Genet, vol. 41, no. 10, pp. 1100-1104. https://doi.org/10.1038/ng.447

TY - JOUR

T1 - IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

AU - Suppiah, Vijayaprakash

AU - Moldovan, Max

AU - Ahlenstiel, Golo

AU - Berg, Thomas

AU - Weltman, Martin

AU - Abate, Maria Lorena

AU - Bassendine, Margaret

AU - Spengler, Ulrich

AU - Dore, Gregory J.

AU - Powell, Elizabeth

AU - Riordan, Stephen

AU - Sheridan, David

AU - Smedile, Antonina

AU - Fragomeli, Vincenzo

AU - Müller, Tobias

AU - Bahlo, Melanie

AU - Stewart, Graeme J.

AU - Booth, David R.

AU - George, Jacob

PY - 2009/10

Y1 - 2009/10

N2 - Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.

AB - Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.

KW - Adult

KW - Antiviral Agents

KW - Australia

KW - Drug Therapy

KW - Combination

KW - Female

KW - Gene Expression Regulation

KW - Genome-Wide Association Study

KW - Genotype

KW - Hepatitis C

KW - Chronic

KW - Humans

KW - Interferon-alpha

KW - Interferons

KW - Interleukins

KW - Male

KW - Middle Aged

KW - Polyethylene Glycols

KW - Polymorphism

KW - Single Nucleotide

KW - Ribavirin

KW - Treatment Outcome

U2 - 10.1038/ng.447

DO - 10.1038/ng.447

M3 - Article

SN - 1546-1718

VL - 41

SP - 1100

EP - 1104

JO - Nat Genet

JF - Nat Genet

IS - 10

ER -

IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

Abstract

Keywords

UN SDGs

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