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Volume 95, Issue 6

IFNL4/IL-28B haplotype structure and its impact on susceptibility to hepatitis C virus and treatment response in the Japanese population Free

Abstract

A new type III interferon, IFN lambda 4 (IFNL4), and its single-nucleotide polymorphism (SNP) ss469415590 causing a frame shift have been recently reported strongly to affect antiviral therapy for chronic hepatitis C virus (HCV) infection in African and Caucasian populations compared to previously reported IL-28B SNPs rs12979860 and rs8099917. To compare the predictability for treatment outcome among those polymorphisms, we estimated haplotype structure of IFNL4/IL-28B consisting of the three SNPs in 4630 Japanese chronic hepatitis C patients and 1122 healthy controls and then compared their impact on response to pegylated-IFN (PEG-IFN) plus ribavirin (RBV) combined therapy in 903 HCV-1b-infected patients. A total of five haplotypes were identified, although two major haplotypes accounted for >99 % of the variation. The SNPs were tightly linked but not in absolute linkage disequilibrium. We could not find any difference in the predictive impact of any of these three SNPs with regard to susceptibility to HCV and treatment response. However, patients with favourable rs8099917 TT, linked to unfavourable genotypes of ss469415590 and rs12979860, showed poor initial viral response compared with those with all favourable genotypes ( = 0.0022). These findings suggest that, in part, ss469415590 and rs12979860 may have better predictive impact on response to PEG-IFN plus RBV therapy in the Japanese population, especially in patients with any of the minor haplotypes consisting of these SNPs.

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© 2014 The Authors
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2014-06-01
2024-04-19
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References

  1. Abe H., Ochi H., Maekawa T., Hayes C. N., Tsuge M., Miki D., Mitsui F., Hiraga N., Imamura M. other authors 2010; Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. J Hepatol 53:439–443 [View Article][PubMed]
     [Google Scholar]
  2. Abe H., Hayes C. N., Ochi H., Maekawa T., Tsuge M., Miki D., Mitsui F., Hiraga N., Imamura M. other authors 2011; IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy. J Hepatol 54:1094–1101 [View Article][PubMed]
     [Google Scholar]
  3. Akuta N., Suzuki F., Sezaki H., Suzuki Y., Hosaka T., Someya T., Kobayashi M., Saitoh S., Watahiki S. other authors 2006; Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load. J Med Virol 78:83–90 [View Article][PubMed]
     [Google Scholar]
  4. Akuta N., Suzuki F., Hirakawa M., Kawamura Y., Yatsuji H., Sezaki H., Suzuki Y., Hosaka T., Kobayashi M. other authors 2009; A matched case-controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response. J Med Virol 81:452–458 [View Article][PubMed]
     [Google Scholar]
  5. Akuta N., Suzuki F., Hirakawa M., Kawamura Y., Yatsuji H., Sezaki H., Suzuki Y., Hosaka T., Kobayashi M. other authors 2010; Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin. Hepatology 52:421–429 [View Article][PubMed]
     [Google Scholar]
  6. Barrett J. C., Fry B., Maller J., Daly M. J. 2005; Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265 [View Article][PubMed]
     [Google Scholar]
  7. Bergmann J. F., Vrolijk J. M., van der Schaar P., Vroom B., van Hoek B., van der Sluys Veer A., de Vries R. A., Verhey E., Hansen B. E. other authors 2007; Gamma-glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-alpha-2b in chronic hepatitis C non-responders. Liver Int 27:1217–1225[PubMed]
     [Google Scholar]
  8. Bibert S., Roger T., Calandra T., Bochud M., Cerny A., Semmo N., Duong F. H., Gerlach T., Malinverni R. other authors 2013; IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J Exp Med 210:1109–1116 [View Article][PubMed]
     [Google Scholar]
  9. Bucci C., von Delft A., Christian A., Flemming V. M., Harrison A., Halliday J., Collier J., Manganis C., Klenerman P. other authors 2013; ‘Favourable’ IL28B polymorphisms are associated with a marked increase in baseline viral load in hepatitis C virus subtype 3a infection and do not predict a sustained virological response after 24 weeks of therapy. J Gen Virol 94:1259–1265 [View Article][PubMed]
     [Google Scholar]
  10. Charlton M. R., Pockros P. J., Harrison S. A. 2006; Impact of obesity on treatment of chronic hepatitis C. Hepatology 43:1177–1186 [View Article][PubMed]
     [Google Scholar]
  11. Chevaliez S., Pawlotsky J. M. 2007; Hepatitis C virus: virology, diagnosis and management of antiviral therapy. World J Gastroenterol 13:2461–2466[PubMed] [CrossRef]
     [Google Scholar]
  12. Davis G. L., Wong J. B., McHutchison J. G., Manns M. P., Harvey J., Albrecht J. 2003; Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 38:645–652 [View Article][PubMed]
     [Google Scholar]
  13. Desmet V. J., Gerber M., Hoofnagle J. H., Manns M., Scheuer P. J. 1994; Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19:1513–1520 [View Article][PubMed]
     [Google Scholar]
  14. Dill M. T., Duong F. H., Vogt J. E., Bibert S., Bochud P. Y., Terracciano L., Papassotiropoulos A., Roth V., Heim M. H. 2011; Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C. Gastroenterology 140:1021–1031, 1031.e10 [View Article][PubMed]
     [Google Scholar]
  15. El-Shamy A., Nagano-Fujii M., Sasase N., Imoto S., Kim S. R., Hotta H. 2008; Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy. Hepatology 48:38–47 [View Article][PubMed]
     [Google Scholar]
  16. Gao B., Hong F., Radaeva S. 2004; Host factors and failure of interferon-alpha treatment in hepatitis C virus. Hepatology 39:880–890 [View Article][PubMed]
     [Google Scholar]
  17. Ge D., Fellay J., Thompson A. J., Simon J. S., Shianna K. V., Urban T. J., Heinzen E. L., Qiu P., Bertelsen A. H. other authors 2009; Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401 [View Article][PubMed]
     [Google Scholar]
  18. Gopal K., Johnson T. C., Gopal S., Walfish A., Bang C. T., Suwandhi P., Pena-Sahdala H. N., Clain D. J., Bodenheimer H. C. Jr, Min A. D. 2006; Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment. Hepatology 44:335–340 [View Article][PubMed]
     [Google Scholar]
  19. Hadziyannis S. J., Sette H. Jr, Morgan T. R., Balan V., Diago M., Marcellin P., Ramadori G., Bodenheimer H. Jr, Bernstein D. other authors 2004; Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140:346–355 [View Article][PubMed]
     [Google Scholar]
  20. Hayes C. N., Kobayashi M., Akuta N., Suzuki F., Kumada H., Abe H., Miki D., Imamura M., Ochi H. other authors 2011; HCV substitutions and IL28B polymorphisms on outcome of peg-interferon plus ribavirin combination therapy. Gut 60:261–267 [View Article][PubMed]
     [Google Scholar]
  21. Honda M., Sakai A., Yamashita T., Nakamoto Y., Mizukoshi E., Sakai Y., Yamashita T., Nakamura M., Shirasaki T. other authors 2010; Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology 139:499–509 [View Article][PubMed]
     [Google Scholar]
  22. Hosking L., Lumsden S., Lewis K., Yeo A., McCarthy L., Bansal A., Riley J., Purvis I., Xu C. F. 2004; Detection of genotyping errors by Hardy-Weinberg equilibrium testing. Eur J Hum Genet 12:395–399 [View Article][PubMed]
     [Google Scholar]
  23. Kawaoka T., Hayes C. N., Ohishi W., Ochi H., Maekawa T., Abe H., Tsuge M., Mitsui F., Hiraga N. other authors 2011; Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b. J Hepatol 54:408–414 [View Article][PubMed]
     [Google Scholar]
  24. Mangia A., Thompson A. J., Santoro R., Piazzolla V., Tillmann H. L., Patel K., Shianna K. V., Mottola L., Petruzzellis D. other authors 2010; An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 139:821–827, e1 [View Article][PubMed]
     [Google Scholar]
  25. Moghaddam A., Melum E., Reinton N., Ring-Larsen H., Verbaan H., Bjøro K., Dalgard O. 2011; IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection. Hepatology 53:746–754 [View Article][PubMed]
     [Google Scholar]
  26. Morgan T. R., O’Brien T. R. 2011; IL28B-genotype testing now and in the era of direct-acting antiviral agents. Clin Gastroenterol Hepatol 9:293–294 [View Article][PubMed]
     [Google Scholar]
  27. Ochi H., Maekawa T., Abe H., Hayashida Y., Nakano R., Imamura M., Hiraga N., Kawakami Y., Aimitsu S. other authors 2011; IL-28B predicts response to chronic hepatitis C therapy–fine-mapping and replication study in Asian populations. J Gen Virol 92:1071–1081 [View Article][PubMed]
     [Google Scholar]
  28. Ohnishi Y., Tanaka T., Ozaki K., Yamada R., Suzuki H., Nakamura Y. 2001; A high-throughput SNP typing system for genome-wide association studies. J Hum Genet 46:471–477 [View Article][PubMed]
     [Google Scholar]
  29. Ohnishi M., Tsuge M., Kohno T., Zhang Y., Abe H., Hyogo H., Kimura Y., Miki D., Hiraga N. other authors 2012; IL28B polymorphism is associated with fatty change in the liver of chronic hepatitis C patients. J Gastroenterol 47:834–844 [View Article][PubMed]
     [Google Scholar]
  30. Pencina M. J., D’Agostino R. B. Sr, D’Agostino R. B. Jr, Vasan R. S. 2008; Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172 [View Article][PubMed]
     [Google Scholar]
  31. Prokunina-Olsson L., Muchmore B., Tang W., Pfeiffer R. M., Park H., Dickensheets H., Hergott D., Porter-Gill P., Mumy A. other authors 2013; A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 45:164–171 [View Article][PubMed]
     [Google Scholar]
  32. Romero-Gómez M., Del Mar Viloria M., Andrade R. J., Salmerón J., Diago M., Fernández-Rodríguez C. M., Corpas R., Cruz M., Grande L. other authors 2005; Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology 128:636–641 [View Article][PubMed]
     [Google Scholar]
  33. Salanti G., Amountza G., Ntzani E. E., Ioannidis J. P. 2005; Hardy-Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. Eur J Hum Genet 13:840–848 [View Article][PubMed]
     [Google Scholar]
  34. Shepard C. W., Finelli L., Alter M. J. 2005; Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 5:558–567 [View Article][PubMed]
     [Google Scholar]
  35. Suppiah V., Moldovan M., Ahlenstiel G., Berg T., Weltman M., Abate M. L., Bassendine M., Spengler U., Dore G. J. other authors 2009; IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nat Genet 41:1100–1104 [View Article][PubMed]
     [Google Scholar]
  36. Tanaka Y., Nishida N., Sugiyama M., Kurosaki M., Matsuura K., Sakamoto N., Nakagawa M., Korenaga M., Hino K. other authors 2009; Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C. Nat Genet 41:1105–1109 [View Article][PubMed]
     [Google Scholar]
  37. Thomas D. L., Thio C. L., Martin M. P., Qi Y., Ge D., O’Huigin C., Kidd J., Kidd K., Khakoo S. I. other authors 2009; Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:798–801 [View Article][PubMed]
     [Google Scholar]
  38. Thompson A. J., Muir A. J., Sulkowski M. S., Ge D., Fellay J., Shianna K. V., Urban T., Afdhal N. H., Jacobson I. M. other authors 2010; Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 139:120–129 [View Article][PubMed]
     [Google Scholar]
  39. Tillmann H. L., Thompson A. J., Patel K., Wiese M., Tenckhoff H., Nischalke H. D., Lokhnygina Y., Kullig U., Göbel U. other authors 2010; A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology 139:1586–1592 [View Article][PubMed]
     [Google Scholar]
  40. Tillmann H. L., Patel K., Muir A. J., Guy C. D., Li J. H., Lao X. Q., Thompson A., Clark P. J., Gardner S. D. other authors 2011; Beneficial IL28B genotype associated with lower frequency of hepatic steatosis in patients with chronic hepatitis C. J Hepatol 55:1195–1200 [View Article][PubMed]
     [Google Scholar]
  41. Urban T. J., Thompson A. J., Bradrick S. S., Fellay J., Schuppan D., Cronin K. D., Hong L., McKenzie A., Patel K. other authors 2010; IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology 52:1888–1896 [View Article][PubMed]
     [Google Scholar]
  42. Yen Y. H., Hung C. H., Hu T. H., Chen C. H., Wu C. M., Wang J. H., Lu S. N., Lee C. M. 2008; Mutations in the interferon sensitivity-determining region (nonstructural 5A amino acid 2209-2248) in patients with hepatitis C-1b infection and correlating response to combined therapy of pegylated interferon and ribavirin. Aliment Pharmacol Ther 27:72–79 [View Article][PubMed]
     [Google Scholar]
  43. Zeuzem S., Franke A., Lee J., Herrmann G., Rüster B., Roth W. K. 1996; Phylogenetic analysis of hepatitis C virus isolates and their correlation to viremia, liver function tests, and histology. Hepatology 24:1003–1009 [View Article][PubMed]
     [Google Scholar]
  44. Zeuzem S., Feinman S. V., Rasenack J., Heathcote E. J., Lai M. Y., Gane E., O’Grady J., Reichen J., Diago M. other authors 2000; Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 343:1666–1672 [View Article][PubMed]
     [Google Scholar]
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IFNL4/IL-28B haplotype structure and its impact on susceptibility to hepatitis C virus and treatment response in the Japanese population
J. Gen. Virol. 95, 1297 (2014); https://doi.org/10.1099/vir.0.060103-0
/content/journal/jgv/10.1099/vir.0.060103-0
/content/journal/jgv/10.1099/vir.0.060103-0
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