title: IFNL4/IL-28B haplotype structure and its impact on susceptibility to hepatitis C virus and treatment response in the Japanese population.
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 (P = 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.
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.|Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.|Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.|Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.|Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Hayashida
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.|Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007564:Japan; D011092:Polyethylene Glycols / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human; C417083:peginterferon alfa-2b