論文

査読有り
2017年9月

Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population

SCIENTIFIC REPORTS
  • Michio Yasunami
  • ,
  • Hitomi Nakamura
  • ,
  • Katsushi Tokunaga
  • ,
  • Minae Kawashima
  • ,
  • Nao Nishida
  • ,
  • Yuki Hitomi
  • ,
  • Minoru Nakamura

7
1
開始ページ
11093
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-017-11148-6
出版者・発行元
NATURE PUBLISHING GROUP

Identification of the primary allele(s) in HLA class II associated diseases remains challenging because of a tight linkage between alleles of HLA-DR and -DQ loci. In the present study, we determined the genotypes of seven HLA loci (HLA-A, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) for 1200 Japanese patients with primary biliary cholangitis and 1196 controls. Observation of recombination derivatives facilitated an evaluation of the effects of individual HLA alleles consisting of disease-prone/disease-resistant HLA haplotypes. Consequently, a primary contribution of DQB1* 06:04 (odds ratio:0.19, p = 1.91 x 10(-22)), DQB1* 03:01 (odds ratio:0.50, p = 6.76 x 10(-10)), DRB1* 08:03 (odds ratio:1.75, p = 1.01 x 10(-7)) and DQB1* 04:01 (odds ratio:1.50, p = 9.20 x 10(-6)) was suggested. Epistasis of the protective DQB1* 06:04 to risk conferred by DRB1* 08:03 was demonstrated by subpopulation analysis, implicating the presence of an active immunological mechanism that alleviates pathogenic autoimmune reactions. Further, the contribution of the aforementioned HLA alleles as well as an HLA-DP allele, DPB1* 02:01 to the association signals of 304 loci among 4103 SNPs in the HLA region at the genome-wide level of significance (p values less than 5 x 10(-8)) was demonstrated by the stepwise exclusion of the individuals possessing these HLA alleles from the comparison.

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1038/s41598-017-11148-6
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28894202
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000410063400022&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/s41598-017-11148-6
  • ISSN : 2045-2322
  • PubMed ID : 28894202
  • Web of Science ID : WOS:000410063400022

エクスポート
BibTeX RIS