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

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Author(s)

    • 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

Abstract

<b>Background:</b> The interleukin-12B gene (<i>IL-12B</i>) 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 <i>IL-12B</i> locus is significantly linked to asthma, as determined by a genome-wide search in the Japanese population.<br> <b>Methods:</b> We sequenced exons 1-8 including parts of the introns and promoter region of <i>IL-12B</i> 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 <i>IL-12B</i> transcriptional activity.<br> <b>Results:</b> <i>IL-12B</i> promoter polymorphism existed as <sup>-2703</sup>CTCTAA/GC and <sup>-2403</sup>T/C alleles, which were linked to each other. Homozygosity for haplotype 1 (<sup>-2703</sup>CTCTAA /<sup>-2403</sup>T) was associated with asthma susceptibility in Japanese children (<i>P</i> < 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 (<sup>-2703</sup>GC /<sup>-2403</sup>C) (<i>P</i> < 0.001). The transcriptional activity of the construct with haplotype 1 was lower than that of the construct with haplotype 2, and the <i>IL-12B</i> transcriptional activity was influenced by the <sup>-2403</sup>T/C allele rather than by the <sup>-2703</sup>CTCTAA/GC allele.<br> <b>Conclusions:</b> Homozygosity for haplotype 1, which is associated with reduced <i>IL-12B</i> transcriptional activity and reduced IL-12 production, is a predisposing factor for asthma susceptibility in Japanese children.<br>

Journal

  • Allergology International

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

    Japanese Society of Allergology

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