PLoS ONE (Jan 2014)

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
https://doi.org/10.1371/journal.pone.0086449
Journal volume & issue
Vol. 9, no. 2
p. e86449

Abstract

Read online

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 = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ∶ 01 (P = 5.22 × 10(-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 = 1.55 × 10(-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.