HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection

Yuka Ochi, Senju Hashimoto, Naoto Kawabe, Michihito Murao, Takuji Nakano, Toshiki Kan, Kazunori Nakaoka, Masashi Ohki, Takamitsu Kurashita, Tomoki Takamura, Sayuri Nomura, Toru Nishikawa, Aiko Fukui, Keisuke Osakabe, Naohiro Ichino, Kentaro Yoshioka

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4 Citations (Scopus)

Abstract

Aim: Genome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. Methods: The SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. Results: In 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core-related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ-glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild-type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels. Conclusion: This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

Original languageEnglish
Pages (from-to)755-766
Number of pages12
JournalHepatology Research
Volume47
Issue number8
DOIs
Publication statusPublished - 01-07-2017

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Chronic Hepatitis B
Virus Diseases
Hepatitis B Surface Antigens
HLA Antigens
Hepatitis B virus
Hepatocellular Carcinoma
Genotype
Genes
Single Nucleotide Polymorphism
Hepatitis B e Antigens
Platelet Count
Nucleosides
Multivariate Analysis
Nucleotides
Hepatitis B Core Antigens
gamma-Glutamyltransferase
Genome-Wide Association Study
Genetic Promoter Regions
DNA
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases

Cite this

Ochi, Yuka ; Hashimoto, Senju ; Kawabe, Naoto ; Murao, Michihito ; Nakano, Takuji ; Kan, Toshiki ; Nakaoka, Kazunori ; Ohki, Masashi ; Kurashita, Takamitsu ; Takamura, Tomoki ; Nomura, Sayuri ; Nishikawa, Toru ; Fukui, Aiko ; Osakabe, Keisuke ; Ichino, Naohiro ; Yoshioka, Kentaro. / HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection. In: Hepatology Research. 2017 ; Vol. 47, No. 8. pp. 755-766.
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title = "HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection",
abstract = "Aim: Genome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. Methods: The SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. Results: In 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core-related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ-glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild-type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels. Conclusion: This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.",
author = "Yuka Ochi and Senju Hashimoto and Naoto Kawabe and Michihito Murao and Takuji Nakano and Toshiki Kan and Kazunori Nakaoka and Masashi Ohki and Takamitsu Kurashita and Tomoki Takamura and Sayuri Nomura and Toru Nishikawa and Aiko Fukui and Keisuke Osakabe and Naohiro Ichino and Kentaro Yoshioka",
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Ochi, Y, Hashimoto, S, Kawabe, N, Murao, M, Nakano, T, Kan, T, Nakaoka, K, Ohki, M, Kurashita, T, Takamura, T, Nomura, S, Nishikawa, T, Fukui, A, Osakabe, K, Ichino, N & Yoshioka, K 2017, 'HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection', Hepatology Research, vol. 47, no. 8, pp. 755-766. https://doi.org/10.1111/hepr.12812

HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection. / Ochi, Yuka; Hashimoto, Senju; Kawabe, Naoto; Murao, Michihito; Nakano, Takuji; Kan, Toshiki; Nakaoka, Kazunori; Ohki, Masashi; Kurashita, Takamitsu; Takamura, Tomoki; Nomura, Sayuri; Nishikawa, Toru; Fukui, Aiko; Osakabe, Keisuke; Ichino, Naohiro; Yoshioka, Kentaro.

In: Hepatology Research, Vol. 47, No. 8, 01.07.2017, p. 755-766.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection

AU - Ochi, Yuka

AU - Hashimoto, Senju

AU - Kawabe, Naoto

AU - Murao, Michihito

AU - Nakano, Takuji

AU - Kan, Toshiki

AU - Nakaoka, Kazunori

AU - Ohki, Masashi

AU - Kurashita, Takamitsu

AU - Takamura, Tomoki

AU - Nomura, Sayuri

AU - Nishikawa, Toru

AU - Fukui, Aiko

AU - Osakabe, Keisuke

AU - Ichino, Naohiro

AU - Yoshioka, Kentaro

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Aim: Genome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. Methods: The SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. Results: In 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core-related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ-glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild-type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels. Conclusion: This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

AB - Aim: Genome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. Methods: The SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. Results: In 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core-related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ-glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild-type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels. Conclusion: This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

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DO - 10.1111/hepr.12812

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