Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean

Nao Nishida, Hiromi Sawai, Kentaro Matsuura, Masaya Sugiyama, SangHoon Ahn, Junyong Park, Shuhei Hige, Jong Hon Kang, Kazuyuki Suzuki, Masayuki Kurosaki, Yasuhiro Asahina, Satoshi Mochida, Masaaki Watanabe, Eiji Tanaka, Masao Honda, Shuichi Kaneko, Etsuro Orito, Yoshito Itoh, Eiji Mita, Akihiro Tamori & 16 others Yoshikazu Murawaki, Yoichi Hiasa, Isao Sakaida, Masaaki Korenaga, Keisuke Hino, Tatsuya Ide, Minae Kawashima, Yoriko Mawatari, Megumi Sageshima, Yuko Ogasawara, Asako Koike, Namiki Izumi, KwangHyub Han, Yasuhito Tanaka, Katsushi Tokunaga, Masashi Mizokami

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P meta = 1.89×10 -12 for rs3077 and P meta = 9.69×10 -10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P meta = 4.40×10 -19 for rs3077 and P meta = 1.28×10 -15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.

Original languageEnglish
Article numbere39175
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - 2012 Jun 21

Fingerprint

HLA-DP Antigens
chronic hepatitis B
Hepatitis B virus
Genome-Wide Association Study
Chronic Hepatitis B
Viruses
Genes
hepatoma
Liver
Hepatocellular Carcinoma
liver cirrhosis
Virus Diseases
Liver Cirrhosis
protective effect
Population
remission
liver diseases
genome-wide association study
infection
Single Nucleotide Polymorphism

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Nishida, Nao ; Sawai, Hiromi ; Matsuura, Kentaro ; Sugiyama, Masaya ; Ahn, SangHoon ; Park, Junyong ; Hige, Shuhei ; Kang, Jong Hon ; Suzuki, Kazuyuki ; Kurosaki, Masayuki ; Asahina, Yasuhiro ; Mochida, Satoshi ; Watanabe, Masaaki ; Tanaka, Eiji ; Honda, Masao ; Kaneko, Shuichi ; Orito, Etsuro ; Itoh, Yoshito ; Mita, Eiji ; Tamori, Akihiro ; Murawaki, Yoshikazu ; Hiasa, Yoichi ; Sakaida, Isao ; Korenaga, Masaaki ; Hino, Keisuke ; Ide, Tatsuya ; Kawashima, Minae ; Mawatari, Yoriko ; Sageshima, Megumi ; Ogasawara, Yuko ; Koike, Asako ; Izumi, Namiki ; Han, KwangHyub ; Tanaka, Yasuhito ; Tokunaga, Katsushi ; Mizokami, Masashi. / Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. In: PLoS One. 2012 ; Vol. 7, No. 6.
@article{d9d5ce945e2548cda0015cd3b55aa5cf,
title = "Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean",
abstract = "Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90{\%} of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P meta = 1.89×10 -12 for rs3077 and P meta = 9.69×10 -10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P meta = 4.40×10 -19 for rs3077 and P meta = 1.28×10 -15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.",
author = "Nao Nishida and Hiromi Sawai and Kentaro Matsuura and Masaya Sugiyama and SangHoon Ahn and Junyong Park and Shuhei Hige and Kang, {Jong Hon} and Kazuyuki Suzuki and Masayuki Kurosaki and Yasuhiro Asahina and Satoshi Mochida and Masaaki Watanabe and Eiji Tanaka and Masao Honda and Shuichi Kaneko and Etsuro Orito and Yoshito Itoh and Eiji Mita and Akihiro Tamori and Yoshikazu Murawaki and Yoichi Hiasa and Isao Sakaida and Masaaki Korenaga and Keisuke Hino and Tatsuya Ide and Minae Kawashima and Yoriko Mawatari and Megumi Sageshima and Yuko Ogasawara and Asako Koike and Namiki Izumi and KwangHyub Han and Yasuhito Tanaka and Katsushi Tokunaga and Masashi Mizokami",
year = "2012",
month = "6",
day = "21",
doi = "10.1371/journal.pone.0039175",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

Nishida, N, Sawai, H, Matsuura, K, Sugiyama, M, Ahn, S, Park, J, Hige, S, Kang, JH, Suzuki, K, Kurosaki, M, Asahina, Y, Mochida, S, Watanabe, M, Tanaka, E, Honda, M, Kaneko, S, Orito, E, Itoh, Y, Mita, E, Tamori, A, Murawaki, Y, Hiasa, Y, Sakaida, I, Korenaga, M, Hino, K, Ide, T, Kawashima, M, Mawatari, Y, Sageshima, M, Ogasawara, Y, Koike, A, Izumi, N, Han, K, Tanaka, Y, Tokunaga, K & Mizokami, M 2012, 'Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean', PLoS One, vol. 7, no. 6, e39175. https://doi.org/10.1371/journal.pone.0039175

Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. / Nishida, Nao; Sawai, Hiromi; Matsuura, Kentaro; Sugiyama, Masaya; Ahn, SangHoon; Park, Junyong; Hige, Shuhei; Kang, Jong Hon; Suzuki, Kazuyuki; Kurosaki, Masayuki; Asahina, Yasuhiro; Mochida, Satoshi; Watanabe, Masaaki; Tanaka, Eiji; Honda, Masao; Kaneko, Shuichi; Orito, Etsuro; Itoh, Yoshito; Mita, Eiji; Tamori, Akihiro; Murawaki, Yoshikazu; Hiasa, Yoichi; Sakaida, Isao; Korenaga, Masaaki; Hino, Keisuke; Ide, Tatsuya; Kawashima, Minae; Mawatari, Yoriko; Sageshima, Megumi; Ogasawara, Yuko; Koike, Asako; Izumi, Namiki; Han, KwangHyub; Tanaka, Yasuhito; Tokunaga, Katsushi; Mizokami, Masashi.

In: PLoS One, Vol. 7, No. 6, e39175, 21.06.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean

AU - Nishida, Nao

AU - Sawai, Hiromi

AU - Matsuura, Kentaro

AU - Sugiyama, Masaya

AU - Ahn, SangHoon

AU - Park, Junyong

AU - Hige, Shuhei

AU - Kang, Jong Hon

AU - Suzuki, Kazuyuki

AU - Kurosaki, Masayuki

AU - Asahina, Yasuhiro

AU - Mochida, Satoshi

AU - Watanabe, Masaaki

AU - Tanaka, Eiji

AU - Honda, Masao

AU - Kaneko, Shuichi

AU - Orito, Etsuro

AU - Itoh, Yoshito

AU - Mita, Eiji

AU - Tamori, Akihiro

AU - Murawaki, Yoshikazu

AU - Hiasa, Yoichi

AU - Sakaida, Isao

AU - Korenaga, Masaaki

AU - Hino, Keisuke

AU - Ide, Tatsuya

AU - Kawashima, Minae

AU - Mawatari, Yoriko

AU - Sageshima, Megumi

AU - Ogasawara, Yuko

AU - Koike, Asako

AU - Izumi, Namiki

AU - Han, KwangHyub

AU - Tanaka, Yasuhito

AU - Tokunaga, Katsushi

AU - Mizokami, Masashi

PY - 2012/6/21

Y1 - 2012/6/21

N2 - Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P meta = 1.89×10 -12 for rs3077 and P meta = 9.69×10 -10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P meta = 4.40×10 -19 for rs3077 and P meta = 1.28×10 -15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.

AB - Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P meta = 1.89×10 -12 for rs3077 and P meta = 9.69×10 -10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P meta = 4.40×10 -19 for rs3077 and P meta = 1.28×10 -15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.

UR - http://www.scopus.com/inward/record.url?scp=84862668325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862668325&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0039175

DO - 10.1371/journal.pone.0039175

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e39175

ER -