IL28B genotype and the expression of ISGs in normal liver

Zoe Raglow, Carly Thoma-Perry, Richard Gilroy, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background & Aims: Both polymorphisms in the IL28B gene locus and ISG expression levels are associated with the outcome of hepatitis C virus (HCV) infection. The two are also interrelated, although the mechanism is unknown. Favourable CC genotype at rs12979860 expresses lower baseline ISG levels and responds better to treatment than unfavourable CT and TT genotypes. Little is known about this relationship in normal, uninfected liver. This study sought to explore this relationship. Methods: Normal human liver specimens (64) and HCV positive human liver specimens (95) were genotyped for IL28B rs12979860 C > T. mRNA levels of ISGs and other relevant genes were studied by qPCR. Results: Most studied ISGs had significantly different expression by IL28B genotype in normal liver. CC genotype expressed the highest levels, CT intermediate and TT the lowest. This is opposite to the pattern seen in HCV patients. Principal component analysis of IL28B genotype and ISG expression further revealed a distinct set of genes correlated with the C allele (ISG15, HTATIP2, LGALS3BP, IRF2 and BCL2) and T allele (IFNα, β, γ, λ3 and CD80). Conclusion: A subset of ISGs was found to be differentially expressed in normal liver by IL28B genotype. This suggests a relationship between IL28B genotype and gene expression before HCV infection.

Original languageEnglish (US)
Pages (from-to)991-998
Number of pages8
JournalLiver International
Volume33
Issue number7
DOIs
StatePublished - Aug 2013

Fingerprint

Genotype
Liver
Hepacivirus
Virus Diseases
Alleles
Genes
Principal Component Analysis
Gene Expression
Messenger RNA
Therapeutics

Keywords

  • Gene expression
  • Hepatitis C virus
  • IL28B
  • Interferon-stimulated genes

ASJC Scopus subject areas

  • Hepatology

Cite this

IL28B genotype and the expression of ISGs in normal liver. / Raglow, Zoe; Thoma-Perry, Carly; Gilroy, Richard; Wan, Yu-Jui Yvonne.

In: Liver International, Vol. 33, No. 7, 08.2013, p. 991-998.

Research output: Contribution to journalArticle

Raglow, Zoe ; Thoma-Perry, Carly ; Gilroy, Richard ; Wan, Yu-Jui Yvonne. / IL28B genotype and the expression of ISGs in normal liver. In: Liver International. 2013 ; Vol. 33, No. 7. pp. 991-998.
@article{3be093b3cd56468d9a160143d3f3bc4f,
title = "IL28B genotype and the expression of ISGs in normal liver",
abstract = "Background & Aims: Both polymorphisms in the IL28B gene locus and ISG expression levels are associated with the outcome of hepatitis C virus (HCV) infection. The two are also interrelated, although the mechanism is unknown. Favourable CC genotype at rs12979860 expresses lower baseline ISG levels and responds better to treatment than unfavourable CT and TT genotypes. Little is known about this relationship in normal, uninfected liver. This study sought to explore this relationship. Methods: Normal human liver specimens (64) and HCV positive human liver specimens (95) were genotyped for IL28B rs12979860 C > T. mRNA levels of ISGs and other relevant genes were studied by qPCR. Results: Most studied ISGs had significantly different expression by IL28B genotype in normal liver. CC genotype expressed the highest levels, CT intermediate and TT the lowest. This is opposite to the pattern seen in HCV patients. Principal component analysis of IL28B genotype and ISG expression further revealed a distinct set of genes correlated with the C allele (ISG15, HTATIP2, LGALS3BP, IRF2 and BCL2) and T allele (IFNα, β, γ, λ3 and CD80). Conclusion: A subset of ISGs was found to be differentially expressed in normal liver by IL28B genotype. This suggests a relationship between IL28B genotype and gene expression before HCV infection.",
keywords = "Gene expression, Hepatitis C virus, IL28B, Interferon-stimulated genes",
author = "Zoe Raglow and Carly Thoma-Perry and Richard Gilroy and Wan, {Yu-Jui Yvonne}",
year = "2013",
month = "8",
doi = "10.1111/liv.12148",
language = "English (US)",
volume = "33",
pages = "991--998",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - IL28B genotype and the expression of ISGs in normal liver

AU - Raglow, Zoe

AU - Thoma-Perry, Carly

AU - Gilroy, Richard

AU - Wan, Yu-Jui Yvonne

PY - 2013/8

Y1 - 2013/8

N2 - Background & Aims: Both polymorphisms in the IL28B gene locus and ISG expression levels are associated with the outcome of hepatitis C virus (HCV) infection. The two are also interrelated, although the mechanism is unknown. Favourable CC genotype at rs12979860 expresses lower baseline ISG levels and responds better to treatment than unfavourable CT and TT genotypes. Little is known about this relationship in normal, uninfected liver. This study sought to explore this relationship. Methods: Normal human liver specimens (64) and HCV positive human liver specimens (95) were genotyped for IL28B rs12979860 C > T. mRNA levels of ISGs and other relevant genes were studied by qPCR. Results: Most studied ISGs had significantly different expression by IL28B genotype in normal liver. CC genotype expressed the highest levels, CT intermediate and TT the lowest. This is opposite to the pattern seen in HCV patients. Principal component analysis of IL28B genotype and ISG expression further revealed a distinct set of genes correlated with the C allele (ISG15, HTATIP2, LGALS3BP, IRF2 and BCL2) and T allele (IFNα, β, γ, λ3 and CD80). Conclusion: A subset of ISGs was found to be differentially expressed in normal liver by IL28B genotype. This suggests a relationship between IL28B genotype and gene expression before HCV infection.

AB - Background & Aims: Both polymorphisms in the IL28B gene locus and ISG expression levels are associated with the outcome of hepatitis C virus (HCV) infection. The two are also interrelated, although the mechanism is unknown. Favourable CC genotype at rs12979860 expresses lower baseline ISG levels and responds better to treatment than unfavourable CT and TT genotypes. Little is known about this relationship in normal, uninfected liver. This study sought to explore this relationship. Methods: Normal human liver specimens (64) and HCV positive human liver specimens (95) were genotyped for IL28B rs12979860 C > T. mRNA levels of ISGs and other relevant genes were studied by qPCR. Results: Most studied ISGs had significantly different expression by IL28B genotype in normal liver. CC genotype expressed the highest levels, CT intermediate and TT the lowest. This is opposite to the pattern seen in HCV patients. Principal component analysis of IL28B genotype and ISG expression further revealed a distinct set of genes correlated with the C allele (ISG15, HTATIP2, LGALS3BP, IRF2 and BCL2) and T allele (IFNα, β, γ, λ3 and CD80). Conclusion: A subset of ISGs was found to be differentially expressed in normal liver by IL28B genotype. This suggests a relationship between IL28B genotype and gene expression before HCV infection.

KW - Gene expression

KW - Hepatitis C virus

KW - IL28B

KW - Interferon-stimulated genes

UR - http://www.scopus.com/inward/record.url?scp=84880142886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880142886&partnerID=8YFLogxK

U2 - 10.1111/liv.12148

DO - 10.1111/liv.12148

M3 - Article

C2 - 23522062

AN - SCOPUS:84880142886

VL - 33

SP - 991

EP - 998

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 7

ER -