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A functional variant in IL12B promoter modulates its expression and associates with increased risk of allergic asthma

Genes & Immunity volume 14, pages 238–243 (2013)Cite this article

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Abstract

The interleukin-12B (IL12B) gene encodes the p40 chain of IL-12, a pro-inflammatory cytokine that antagonizes Th2 phenotype and, hence, may have a critical role in the pathogenesis of allergic asthma. In this report, we describe the identification of a novel IL12B promoter polymorphism (T-to-A exchange) at position −536. The IL12B −536AA genotype was significantly associated with asthma in the Chinese populations (P=0.011, odds ratio=2.227). The risk-associated A allele was linked to reduced expression of IL12B mRNA levels and IL12B production in asthmatic patients. Luciferase reporter assay provided evidence that risk-associated A allele reduced the promoter activity of IL12B gene compared with those of the promoter containing the protective T allele. We further observed that decreasing binding effects between the risk alleles A of IL12B and CCAAT/enhancer binding protein alpha (C/EBPα) through A allele sequence mediated streptavidin-conjugated agarose pulldown and biotin-labelled A allele mediated electrophoretic mobility shift assay. We also observed additive effects of the risk alleles of IL12B and decreased mRNA levels of C/EBPα in asthmatic patients. Therefore, we postulated that the presence of −536A allele in IL12B promoter could predispose to the development of allergic asthma.

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Acknowledgements

This study was sponsored by the Startup Package of Shanghai Zhongcheng translational-medicine Co., Ltd.

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  1. Z Xu and L Pei: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Diagnosis, Shanghai Zhongcheng Translational-medicine Co., Ltd, Shanghai, China

    Z Xu, L Pei & F Zhang

  2. Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Z Xu

  3. Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    X Hu & Y Gui

  4. Department of Respiratory Disease of Renji Hospital, Affiliated with School of Medicine, Shanghai Jiaotong University, Shanghai, China

    L Wang

  5. The First Hospital, Medical School, Zhengzhou University, Zhengzhou, Henan, China

    B Wu

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  1. Z Xu
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Correspondence to Z Xu.

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Xu, Z., Pei, L., Zhang, F. et al. A functional variant in IL12B promoter modulates its expression and associates with increased risk of allergic asthma. Genes Immun 14, 238–243 (2013). https://doi.org/10.1038/gene.2013.13

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