New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

Nao Nishida; Hiromi Sawai; Koichi Kashiwase; Mutsuhiko Minami; Masaya Sugiyama; Wai Kay Seto; Man Fung Yuen; Nawarat Posuwan; Yong Poovorawan; Sang Hoon Ahn; Kwang Hyub Han; Kentaro Matsuura; Yasuhito Tanaka; Masayuki Kurosaki; Yasuhiro Asahina; Namiki Izumi; Jong Hon Kang; Shuhei Hige; Tatsuya Ide Kazuhide Yamamoto; Isao Sakaida; Yoshikazu Murawaki; Yoshito Itoh; Akihiro Tamori; Etsuro Orito; Yoichi Hiasa; Masao Honda; Shuichi Kaneko; Eiji Mita; Kazuyuki Suzuki; Keisuke Hino; Eiji Tanaka; Satoshi Mochida; Masaaki Watanabe; Yuichiro Eguchi; Naohiko Masaki; Kazumoto Murata; Masaaki Korenaga; Yoriko Mawatari; Jun Ohashi; Minae Kawashima; Katsushi Tokunaga; Masashi Mizokami

doi:10.1371/journal.pone.0086449

New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

Nao Nishida, Hiromi Sawai, Koichi Kashiwase, Mutsuhiko Minami, Masaya Sugiyama, Wai Kay Seto, Man Fung Yuen, Nawarat Posuwan, Yong Poovorawan, Sang Hoon Ahn, Kwang Hyub Han, Kentaro Matsuura, Yasuhito Tanaka, Masayuki Kurosaki, Yasuhiro Asahina, Namiki Izumi, Jong Hon Kang, Shuhei Hige, Tatsuya Ide Kazuhide Yamamoto, Isao SakaidaYoshikazu Murawaki, Yoshito Itoh, Akihiro Tamori, Etsuro Orito, Yoichi Hiasa, Masao Honda, Shuichi Kaneko, Eiji Mita, Kazuyuki Suzuki, Keisuke Hino, Eiji Tanaka, Satoshi Mochida, Masaaki Watanabe, Yuichiro Eguchi, Naohiko Masaki, Kazumoto Murata, Masaaki Korenaga, Yoriko Mawatari, Jun Ohashi, Minae Kawashima, Katsushi Tokunaga, Masashi Mizokami

Department of Internal Medicine

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Abstract

Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09:01 (P = 1.36x10^-6; OR = 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02:01 (P = 5.22x10 ^-6; OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02:01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55x10^-7; OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.

Original language	English
Article number	e86449
Journal	PloS one
Volume	9
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0086449
Publication status	Published - 2014 Feb 10

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Nishida, N., Sawai, H., Kashiwase, K., Minami, M., Sugiyama, M., Seto, W. K., Yuen, M. F., Posuwan, N., Poovorawan, Y., Ahn, S. H., Han, K. H., Matsuura, K., Tanaka, Y., Kurosaki, M., Asahina, Y., Izumi, N., Kang, J. H., Hige, S., Yamamoto, T. I. K., ... Mizokami, M. (2014). New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia. PloS one, 9(2), [e86449]. https://doi.org/10.1371/journal.pone.0086449

Nishida, Nao ; Sawai, Hiromi ; Kashiwase, Koichi ; Minami, Mutsuhiko ; Sugiyama, Masaya ; Seto, Wai Kay ; Yuen, Man Fung ; Posuwan, Nawarat ; Poovorawan, Yong ; Ahn, Sang Hoon ; Han, Kwang Hyub ; Matsuura, Kentaro ; Tanaka, Yasuhito ; Kurosaki, Masayuki ; Asahina, Yasuhiro ; Izumi, Namiki ; Kang, Jong Hon ; Hige, Shuhei ; Yamamoto, Tatsuya Ide Kazuhide ; Sakaida, Isao ; Murawaki, Yoshikazu ; Itoh, Yoshito ; Tamori, Akihiro ; Orito, Etsuro ; Hiasa, Yoichi ; Honda, Masao ; Kaneko, Shuichi ; Mita, Eiji ; Suzuki, Kazuyuki ; Hino, Keisuke ; Tanaka, Eiji ; Mochida, Satoshi ; Watanabe, Masaaki ; Eguchi, Yuichiro ; Masaki, Naohiko ; Murata, Kazumoto ; Korenaga, Masaaki ; Mawatari, Yoriko ; Ohashi, Jun ; Kawashima, Minae ; Tokunaga, Katsushi ; Mizokami, Masashi. / New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia. In: PloS one. 2014 ; Vol. 9, No. 2.

@article{c22a214121d64b3695c30caba7edc203,

title = "New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia",

abstract = "Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09:01 (P = 1.36x10-6; OR = 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02:01 (P = 5.22x10 -6; OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02:01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55x10-7; OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.",

author = "Nao Nishida and Hiromi Sawai and Koichi Kashiwase and Mutsuhiko Minami and Masaya Sugiyama and Seto, {Wai Kay} and Yuen, {Man Fung} and Nawarat Posuwan and Yong Poovorawan and Ahn, {Sang Hoon} and Han, {Kwang Hyub} and Kentaro Matsuura and Yasuhito Tanaka and Masayuki Kurosaki and Yasuhiro Asahina and Namiki Izumi and Kang, {Jong Hon} and Shuhei Hige and Yamamoto, {Tatsuya Ide Kazuhide} and Isao Sakaida and Yoshikazu Murawaki and Yoshito Itoh and Akihiro Tamori and Etsuro Orito and Yoichi Hiasa and Masao Honda and Shuichi Kaneko and Eiji Mita and Kazuyuki Suzuki and Keisuke Hino and Eiji Tanaka and Satoshi Mochida and Masaaki Watanabe and Yuichiro Eguchi and Naohiko Masaki and Kazumoto Murata and Masaaki Korenaga and Yoriko Mawatari and Jun Ohashi and Minae Kawashima and Katsushi Tokunaga and Masashi Mizokami",

year = "2014",

month = feb,

day = "10",

doi = "10.1371/journal.pone.0086449",

language = "English",

volume = "9",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "2",

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Nishida, N, Sawai, H, Kashiwase, K, Minami, M, Sugiyama, M, Seto, WK, Yuen, MF, Posuwan, N, Poovorawan, Y, Ahn, SH , Han, KH, Matsuura, K, Tanaka, Y, Kurosaki, M, Asahina, Y, Izumi, N, Kang, JH, Hige, S, Yamamoto, TIK, Sakaida, I, Murawaki, Y, Itoh, Y, Tamori, A, Orito, E, Hiasa, Y, Honda, M, Kaneko, S, Mita, E, Suzuki, K, Hino, K, Tanaka, E, Mochida, S, Watanabe, M, Eguchi, Y, Masaki, N, Murata, K, Korenaga, M, Mawatari, Y, Ohashi, J, Kawashima, M, Tokunaga, K & Mizokami, M 2014, 'New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia', PloS one, vol. 9, no. 2, e86449. https://doi.org/10.1371/journal.pone.0086449

New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia. / Nishida, Nao; Sawai, Hiromi; Kashiwase, Koichi; Minami, Mutsuhiko; Sugiyama, Masaya; Seto, Wai Kay; Yuen, Man Fung; Posuwan, Nawarat; Poovorawan, Yong; Ahn, Sang Hoon ; Han, Kwang Hyub; Matsuura, Kentaro; Tanaka, Yasuhito; Kurosaki, Masayuki; Asahina, Yasuhiro; Izumi, Namiki; Kang, Jong Hon; Hige, Shuhei; Yamamoto, Tatsuya Ide Kazuhide; Sakaida, Isao; Murawaki, Yoshikazu; Itoh, Yoshito; Tamori, Akihiro; Orito, Etsuro; Hiasa, Yoichi; Honda, Masao; Kaneko, Shuichi; Mita, Eiji; Suzuki, Kazuyuki; Hino, Keisuke; Tanaka, Eiji; Mochida, Satoshi; Watanabe, Masaaki; Eguchi, Yuichiro; Masaki, Naohiko; Murata, Kazumoto; Korenaga, Masaaki; Mawatari, Yoriko; Ohashi, Jun; Kawashima, Minae; Tokunaga, Katsushi; Mizokami, Masashi.

In: PloS one, Vol. 9, No. 2, e86449, 10.02.2014.

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

TY - JOUR

T1 - New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

AU - Nishida, Nao

AU - Sawai, Hiromi

AU - Kashiwase, Koichi

AU - Minami, Mutsuhiko

AU - Sugiyama, Masaya

AU - Seto, Wai Kay

AU - Yuen, Man Fung

AU - Posuwan, Nawarat

AU - Poovorawan, Yong

AU - Ahn, Sang Hoon

AU - Han, Kwang Hyub

AU - Matsuura, Kentaro

AU - Tanaka, Yasuhito

AU - Kurosaki, Masayuki

AU - Asahina, Yasuhiro

AU - Izumi, Namiki

AU - Kang, Jong Hon

AU - Hige, Shuhei

AU - Yamamoto, Tatsuya Ide Kazuhide

AU - Sakaida, Isao

AU - Murawaki, Yoshikazu

AU - Itoh, Yoshito

AU - Tamori, Akihiro

AU - Orito, Etsuro

AU - Hiasa, Yoichi

AU - Honda, Masao

AU - Kaneko, Shuichi

AU - Mita, Eiji

AU - Suzuki, Kazuyuki

AU - Hino, Keisuke

AU - Tanaka, Eiji

AU - Mochida, Satoshi

AU - Watanabe, Masaaki

AU - Eguchi, Yuichiro

AU - Masaki, Naohiko

AU - Murata, Kazumoto

AU - Korenaga, Masaaki

AU - Mawatari, Yoriko

AU - Ohashi, Jun

AU - Kawashima, Minae

AU - Tokunaga, Katsushi

AU - Mizokami, Masashi

PY - 2014/2/10

Y1 - 2014/2/10

N2 - Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09:01 (P = 1.36x10-6; OR = 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02:01 (P = 5.22x10 -6; OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02:01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55x10-7; OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.

AB - Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09:01 (P = 1.36x10-6; OR = 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02:01 (P = 5.22x10 -6; OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02:01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55x10-7; OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.

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ER -

New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

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