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.
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 IL28Brs12979860 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 HCVpatients. 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.
Authors: E Zuckerman; T Zuckerman; D Sahar; S Streichman; D Attias; E Sabo; D Yeshurun; J Rowe Journal: Br J Haematol Date: 2001-02 Impact factor: 6.998
Authors: Christoph Sarrazin; Simone Susser; Alexandra Doehring; Christian Markus Lange; Tobias Müller; Christina Schlecker; Eva Herrmann; Jörn Lötsch; Thomas Berg Journal: J Hepatol Date: 2010-09-22 Impact factor: 25.083
Authors: Michael T Dill; Francois H T Duong; Julia E Vogt; Stéphanie Bibert; Pierre-Yves Bochud; Luigi Terracciano; Andreas Papassotiropoulos; Volker Roth; Markus H Heim Journal: Gastroenterology Date: 2010-11-25 Impact factor: 22.682
Authors: 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 Journal: Nat Genet Date: 2009-09-13 Impact factor: 38.330
Authors: P S Vaughan; F Aziz; A J van Wijnen; S Wu; H Harada; T Taniguchi; K J Soprano; J L Stein; G S Stein Journal: Nature Date: 1995-09-28 Impact factor: 49.962
Authors: Nikolaos K Gatselis; Kalliopi Zachou; Asterios Saitis; Maria Samara; George N Dalekos Journal: World J Gastroenterol Date: 2014-03-21 Impact factor: 5.742
Authors: Rikke Olesen; Selena Vigano; Thomas A Rasmussen; Ole S Søgaard; Zhengyu Ouyang; Maria Buzon; Arman Bashirova; Mary Carrington; Sarah Palmer; Christel R Brinkmann; Xu G Yu; Lars Østergaard; Martin Tolstrup; Mathias Lichterfeld Journal: J Virol Date: 2015-07-29 Impact factor: 5.103
Authors: Ulrich Spengler; Hans Dieter Nischalke; Jacob Nattermann; Christian P Strassburg Journal: World J Gastroenterol Date: 2013-11-28 Impact factor: 5.742
Authors: Mohammed Eslam; Ahmed M Hashem; Reynold Leung; Manuel Romero-Gomez; Thomas Berg; Gregory J Dore; Henry L K Chan; William L Irving; David Sheridan; Maria L Abate; Leon A Adams; Alessandra Mangia; Martin Weltman; Elisabetta Bugianesi; Ulrich Spengler; Olfat Shaker; Janett Fischer; Lindsay Mollison; Wendy Cheng; Elizabeth Powell; Jacob Nattermann; Stephen Riordan; Duncan McLeod; Nicola J Armstrong; Mark W Douglas; Christopher Liddle; David R Booth; Jacob George; Golo Ahlenstiel Journal: Nat Commun Date: 2015-03-05 Impact factor: 14.919
Authors: Yaneli Juárez-Vicuña; Julia Pérez-Ramos; Laura Adalid-Peralta; Fausto Sánchez; Laura Aline Martínez-Martínez; María Del Carmen Ortiz-Segura; Edgar Pichardo-Ontiveros; Adrián Hernández-Díazcouder; Luis M Amezcua-Guerra; Julian Ramírez-Bello; Fausto Sánchez-Muñoz Journal: Front Genet Date: 2021-06-02 Impact factor: 4.599