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; Sang Hoon Ahn; Jun Yong 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; Yoshikazu Murawaki; Yoichi Hiasa; Isao Sakaida; Masaaki Korenaga; Keisuke Hino; Tatsuya Ide; Minae Kawashima; Yoriko Mawatari; Megumi Sageshima; Yuko Ogasawara; Asako Koike; Namiki Izumi; Kwang Hyub Han; Yasuhito Tanaka; Katsushi Tokunaga; Masashi Mizokami

doi: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

Nao Nishida, Hiromi Sawai, Kentaro Matsuura, Masaya Sugiyama, Sang Hoon Ahn, Jun Yong 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 TamoriYoshikazu Murawaki, Yoichi Hiasa, Isao Sakaida, Masaaki Korenaga, Keisuke Hino, Tatsuya Ide, Minae Kawashima, Yoriko Mawatari, Megumi Sageshima, Yuko Ogasawara, Asako Koike, Namiki Izumi, Kwang Hyub Han, Yasuhito Tanaka, Katsushi Tokunaga, Masashi Mizokami

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

122 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 language	English
Article number	e39175
Journal	PloS one
Volume	7
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0039175
Publication status	Published - 2012 Jun 21

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Nishida, N., Sawai, H., Matsuura, K., Sugiyama, M., Ahn, S. H., Park, J. Y., Hige, S., Kang, J. H., Suzuki, K., Kurosaki, M., Asahina, Y., Mochida, S., Watanabe, M., Tanaka, E., Honda, M., Kaneko, S., Orito, E., Itoh, Y., Mita, E., ... 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, 7(6), [e39175]. https://doi.org/10.1371/journal.pone.0039175

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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 Ahn, {Sang Hoon} and Park, {Jun Yong} 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 Han, {Kwang Hyub} and Yasuhito Tanaka and Katsushi Tokunaga and Masashi Mizokami",

year = "2012",

month = jun,

day = "21",

doi = "10.1371/journal.pone.0039175",

language = "English",

volume = "7",

journal = "PLoS One",

issn = "1932-6203",

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Nishida, N, Sawai, H, Matsuura, K, Sugiyama, M, Ahn, SH , Park, JY, 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, KH, 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

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, Sang Hoon

AU - Park, Jun Yong

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, Kwang Hyub

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

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U2 - 10.1371/journal.pone.0039175

DO - 10.1371/journal.pone.0039175

M3 - Article

C2 - 22737229

AN - SCOPUS:84862668325

SN - 1932-6203

VL - 7

JO - PLoS One

JF - PLoS One

IS - 6

M1 - e39175

ER -

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

Abstract

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