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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 languageEnglish
Article numbere86449
JournalPloS one
Volume9
Issue number2
DOIs
Publication statusPublished - 2014 Feb 10

    Fingerprint

All Science Journal Classification (ASJC) codes

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

Cite this

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