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A thymine–adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

An Erratum to this article was published on 25 December 2015

Abstract

Background

Genome-wide association studies have revealed several single-nucleotide polymorphisms around interleukin 28B (IL28B) that are strongly associated with hepatitis C virus (HCV) clearance. However, their predictive value is not perfect, which suggests that other genetic factors may also be involved in HCV clearance. We previously reported a wide variation in the length of a thymine–adenine (TA) dinucleotide repeat in the promoter region of IL28B and that the transcriptional activity of the promoter increased gradually in a TA repeat length-dependent manner.

Methods

We determined the length of the TA repeats of 1,060 Japanese and 201 African-American samples to investigate the relation to spontaneous HCV clearance.

Results

The distribution of the TA repeats greatly differed between the two ethnicities. The variation ranged from 10 to 18 repeats, and the most frequent allele, 12, accounted for over 80 % for Japanese. The African-American data showed a gently sloping distribution, and the allele with six repeats was detected only in the African-American sample. The TA repeats 11 or greater were correlated with spontaneous clearance. Multiple logistic regression analysis extracted the genotype of the TA repeats as an independent factor in both the Japanese [p = 0.0004, odds ratio (OR) = 13.02 95 % confidence interval (CI) = 2.59–237.0] and African-American (p = 0.027, OR = 3.70 95 % CI = 1.16–11.8) populations.

Conclusions

A long TA repeat in the promoter region of IL28B was associated with spontaneous HCV clearance. Although its efficacy may be limited in Japanese population because of its allele distribution, this novel genetic factor will be useful for predicting HCV clearance especially for the African Americans.

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Abbreviations

IFN:

Interferon

IL28B:

Interleukin 28B

HCV:

Hepatitis C virus

NPV:

Negative predictive value

PEG:

Pegylated

PPV:

Positive predictive value

RBV:

Ribavirin

SNP:

Single-nucleotide polymorphism

UGT:

Uridine diphosphoglucuronosyl transferase

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Acknowledgments

This work was supported by grants from the National Center for Global Health and Medicine of Japan (22-108, 25-202), from the Japanese Ministry of Health, Labor and Welfare (H23-007), and from the Japanese Ministry of Education, Culture, Sports, and Science (No. 22590750). We are also grateful to all the technical staffs of Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine for their excellent lab works on genotyping the SNPs of IL28B and TA repeat.

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

    Authors and Affiliations

    1. Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan

      Satoshi Hiramine, Masaya Sugiyama, Masaaki Korenaga, Kazumoto Murata, Naohiko Masaki & Masashi Mizokami

    2. General Internal Medicine Department, Kyushu University Hospital, Fukuoka, 812-8582, Japan

      Satoshi Hiramine, Norihiro Furusyo & Jun Hayashi

    3. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan

      Hirofumi Uto, Akio Ido & Hirohito Tsubouchi

    4. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, 990-9585, Japan

      Hisayoshi Watanabe & Yoshiyuki Ueno

    5. Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA

      David L. Thomas

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    1. Satoshi Hiramine
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    Correspondence to Masashi Mizokami.

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    S. Hiramine and M. Sugiyama contributed equally to this work.

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    Hiramine, S., Sugiyama, M., Furusyo, N. et al. A thymine–adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus. J Gastroenterol 50, 1069–1077 (2015). https://doi.org/10.1007/s00535-015-1056-1

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