IL-12B Promoter Polymorphism Associated with Asthma and IL-12B Transcriptional Activity

• Tatebayashi Koji

  Department of Pediatrics, Graduate School of Medicine, Gifu University

• Matsui Eiko

  Department of Pediatrics, Graduate School of Medicine, Gifu University

• Kaneko Hideo

  Department of Pediatrics, Graduate School of Medicine, Gifu University

• Fukao Toshiyuki

  Department of Pediatrics, Graduate School of Medicine, Gifu University

• Kasahara Kimiko

  Department of Pediatrics, Graduate School of Medicine, Gifu University

• Kondo Naomi

  Department of Pediatrics, Graduate School of Medicine, Gifu University

抄録

Background: The interleukin-12B gene (IL-12B) encodes the p40 chain of interleukin-12 (IL-12), which promotes cell-mediated Th1 responses and the production of interferon-gamma (IFN-γ) that downregulates IgE production. Chromosome 5q31-q33 near the IL-12B locus is significantly linked to asthma, as determined by a genome-wide search in the Japanese population.<br> Methods: We sequenced exons 1-8 including parts of the introns and promoter region of IL-12B in asthmatic patients and healthy controls. We examined plasma IL-12 concentrations, IL-12 production by Derf1-stimulated peripheral blood mononuclear cells (PBMCs) and the IL-12B transcriptional activity.<br> Results: IL-12B promoter polymorphism existed as ^-2703CTCTAA/GC and ^-2403T/C alleles, which were linked to each other. Homozygosity for haplotype 1 (^-2703CTCTAA /^-2403T) was associated with asthma susceptibility in Japanese children (P < 0.001). Both plasma IL-12 concentrations and IL-12 production by Derf1-stimulated PBMCs in the subjects with homozygotes for haplotype 1 were lower than those with homozygotes for haplotype 2 (^-2703GC /^-2403C) (P < 0.001). The transcriptional activity of the construct with haplotype 1 was lower than that of the construct with haplotype 2, and the IL-12B transcriptional activity was influenced by the ^-2403T/C allele rather than by the ^-2703CTCTAA/GC allele.<br> Conclusions: Homozygosity for haplotype 1, which is associated with reduced IL-12B transcriptional activity and reduced IL-12 production, is a predisposing factor for asthma susceptibility in Japanese children.<br>

収録刊行物

• Allergology International

  Allergology International 54 (3), 451-459, 2005

  一般社団法人日本アレルギー学会

キーワード

• asthma
• IgE
• interferon-gamma
• interleukin-12B promoter polymorphism

詳細情報

• CRID: 1390282679608640896
• NII論文ID: 130004476850
• DOI: 10.2332/allergolint.54.451
• ISSN: 14401592
• ISSN: 13238930
• Web Site: http://api.elsevier.com/content/article/PII:S1323893015310583?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1323893015310583?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2006293561
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可