<i>ORMDL3/GSDMB</i> genotype as a risk factor for early-onset adult asthma is linked to total serum IgE levels but not to allergic sensitization

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  • Kitazawa Haruna
    Department of Pulmonary Medicine, University of Tsukuba
  • Masuko Hironori
    Department of Pulmonary Medicine, University of Tsukuba
  • Kanazawa Jun
    Department of Pulmonary Medicine, University of Tsukuba National Hospital Organization Ibarakihigashi National Hospital
  • Shigemasa Rie
    Department of Pulmonary Medicine, University of Tsukuba
  • Hyodo Kentaro
    Department of Pulmonary Medicine, University of Tsukuba National Hospital Organization Ibarakihigashi National Hospital
  • Yamada Hideyasu
    Department of Pulmonary Medicine, University of Tsukuba
  • Yatagai Yohei
    Department of Pulmonary Medicine, University of Tsukuba
  • Kaneko Yoshiko
    Department of Pulmonary Medicine, University of Tsukuba
  • Iijima Hiroaki
    Tsukuba Medical Center
  • Naito Takashi
    Tsukuba Medical Center
  • Saito Takefumi
    National Hospital Organization Ibarakihigashi National Hospital
  • Noguchi Emiko
    Department of Medical Genetics, University of Tsukuba
  • Konno Satoshi
    Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University
  • Hirota Tomomitsu
    Research Center for Medical Science, The Jikei University School of Medicine
  • Tamari Mayumi
    Research Center for Medical Science, The Jikei University School of Medicine
  • Sakamoto Tohru
    Department of Pulmonary Medicine, University of Tsukuba
  • Hizawa Nobuyuki
    Department of Pulmonary Medicine, University of Tsukuba

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  • ORMDL3/GSDMB genotype as a risk factor for early-onset adult asthma is linked to total serum IgE levels but not to allergic sensitization

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Abstract

<p>Background: An orosomucoid-like 3 (ORMDL3)/gasdermin B (GSDMB) gene locus on chromosome 17q is consistently associated with childhood-onset asthma, which is highly atopic. As some evidence suggests the relationship between asthma and allergic sensitization reflects asthma patient susceptibility to augmented IgE responses driven by common environmental allergens rather than an increased asthma risk after allergen exposure, we aimed to determine any relationships between this locus region and childhood-onset adult asthma with regard to serum total IgE levels or allergic sensitization.</p><p>Methods: We conducted a case–control association study using three independent Japanese populations (3869 total adults) and analyzed the ORs for association of rs7216389, an expression quantitative trait locus for ORMDL3/GSDMB, with adult asthma according to onset age. Additionally, associations between the rs7216389 genotype and total serum IgE levels or allergic sensitization was examined.</p><p>Results: Rs7216389 was associated with both childhood-onset adult asthma (OR for asthmatic patients afflicted at the age of 10 years or younger = 1.61, p = 0.00021) and asthmatic patients with higher levels of total serum IgE (OR for asthmatic patients with IgE ≥1000IU/mL = 1.55, p = 0.0033). In both healthy controls and in the combined healthy and asthmatic individuals, rs7216389 was correlated with increased total serum IgE levels (p < 0.0005), but not allergic sensitization (p > 0.1).</p><p>Conclusions: ORMDL3/GSDMB is an important susceptibility gene for childhood-onset adult asthma in Japanese populations and this association is linked to elevated total serum IgE levels but not to allergic sensitization.</p>

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