論文

査読有り
2017年10月

HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype

PLOS ONE
  • Shomi Oka
  • ,
  • Hiroshi Furukawa
  • ,
  • Michio Yasunami
  • ,
  • Aya Kawasaki
  • ,
  • Hitomi Nakamura
  • ,
  • Minoru Nakamura
  • ,
  • Atsumasa Komori
  • ,
  • Seigo Abiru
  • ,
  • Shinya Nagaoka
  • ,
  • Satoru Hashimoto
  • ,
  • Atsushi Naganuma
  • ,
  • Noriaki Naeshiro
  • ,
  • Kaname Yoshizawa
  • ,
  • Haruhiro Yamashita
  • ,
  • Keisuke Ario
  • ,
  • Hajime Ohta
  • ,
  • Hironori Sakai
  • ,
  • Iwao Yabuuchi
  • ,
  • Atsushi Takahashi
  • ,
  • Kazumichi Abe
  • ,
  • Hiroshi Yatsuhashi
  • ,
  • Shigeto Tohma
  • ,
  • Hiromasa Ohira
  • ,
  • Naoyuki Tsuchiya
  • ,
  • Kiyoshi Migita

12
10
開始ページ
e0187325
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0187325
出版者・発行元
PUBLIC LIBRARY SCIENCE

Objective
Autoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH. HLA-DRB1* 03: 01 and * 04: 01 are associated with type 1 AIH in European and * 04: 05 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.
Methods
HLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.
Results
The predisposing association of DRB1*04: 01 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62-5.43), DRB1*04: 05 (P = 1.89x10(-21), Pc = 5.86x10(-20), OR 3.41, 95% CI 2.65-4.38), and DQB1*04: 01 (P = 4.66x10(-18), Pc = 6.99x10(-17), OR 3.89, 95% CI 2.84-5.33) and the protective association of DRB1*13: 02 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32-0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12x10(-9), OR 3.52, 95% CI 2.34-5.29). Susceptible diplotypes were DRB1*04: 05-DQB1*04: 01/DRB1*08: 02-DQB1*03: 02 (P = 0.0004, OR 24.77, 95% CI 1.45-424.31) and DRB1*04: 05-DQB1*04: 01/DRB1*08: 03-DQB1*06: 01 (P = 1.18x10(-6), OR 10.64, 95% CI 3.19-35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*04: 05 than without.
Conclusions
The important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQ alpha-beta heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes.

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0187325
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29088299
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000414088900066&DestApp=WOS_CPL
ID情報
  • DOI : 10.1371/journal.pone.0187325
  • ISSN : 1932-6203
  • PubMed ID : 29088299
  • Web of Science ID : WOS:000414088900066

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