Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 47, Issue 5, pp 596-605

First online:

Association of two polymorphisms of the IL28B gene with viral factors and treatment response in 1,518 patients infected with hepatitis C virus

  • Mariko KobayashiAffiliated withResearch Institute for Hepatology, Toranomon HospitalDepartment of Hepatology, Toranomon Hospital Email author 
  • , Fumitaka SuzukiAffiliated withDepartment of Hepatology, Toranomon Hospital
  • , Norio AkutaAffiliated withDepartment of Hepatology, Toranomon Hospital
  • , Hitomi SezakiAffiliated withDepartment of Hepatology, Toranomon Hospital
  • , Yoshiyuki SuzukiAffiliated withDepartment of Hepatology, Toranomon Hospital
  • , Tetsuya HosakaAffiliated withDepartment of Hepatology, Toranomon Hospital
  • , Yusuke KawamuraAffiliated withDepartment of Hepatology, Toranomon Hospital
  • , Masahiro KobayashiAffiliated withDepartment of Hepatology, Toranomon Hospital
  • , Satoshi SaitohAffiliated withDepartment of Hepatology, Toranomon Hospital
    • , Yasuji AraseAffiliated withDepartment of Hepatology, Toranomon Hospital
    • , Kenji IkedaAffiliated withDepartment of Hepatology, Toranomon Hospital
    • , Kazuaki ChayamaAffiliated withDivision of Frontier Medical Science, Department of Medical and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University
    • , Yuzo MiyakawaAffiliated withMiyakawa Memorial Research Foundation
    • , Hiromitsu KumadaAffiliated withDepartment of Hepatology, Toranomon Hospital

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Abstract

Background

Two nucleotide polymorphisms of the interleukin-28B (IL28B) gene, at rs8099917 and rs12979860, influence the response to interferon (IFN)-based therapies in patients infected with hepatitis C virus (HCV) of genotype 1. We aimed to investigate whether these polymorphisms showed complete linkage in Japanese patients.

Methods

A total of 1,518 Japanese patients infected with HCV were genotyped for the two IL28B loci, and the two sets of genotypes were compared.

Results

TT at rs8099917 and CC at rs12979860 were detected in 77.7 and 76.8%, respectively, of the 1,518 patients and TG/GG and CT/TT were detected in 22.3 and 23.2%. These two sets of IL28B genotype stood in strong linkage disequilibrium (r 2 = 0.98). Discordance between the two IL28B polymorphisms occurred in 16 (1.1%) patients, and 13 (0.9%) of them possessed IFN-sensitive TT at rs8099917 and IFN-resistant CT at rs12979860. Three of these 13 patients had HCV of genotype 1b and had received pegylated-interferon and ribavirin, and none of them gained a sustained virological response. At rs8099917, IFN-resistant TG/GG were more frequent in patients infected with HCV of genotype 1 than in those infected with HCV of genotype 2 [258/1,046 (24.7%) vs. 75/441 (17.0%), p = 0.001]. The response to pegylated-interferon/ribavirin in 279 patients who were infected with HCV-1 and the response to IFN monotherapy in 361 patients who were infected with HCV-1 , was higher in those with TT than in those with TG/GG at rs8099917, as well as being higher in those with CC than in those with CT/TT at rs12979860 (p < 0.001).

Conclusions

Linkage disequilibrium between two IL28B polymorphisms at rs8099917 and rs12979860 is strong in Japanese HCV patients, but there are some discrepancies between the two sets of genotypes.

Keywords

Hepatitis C virus Chronic hepatitis C Interleukin-28B gene Interferon Single nucleotide polymorphism