EFFECTS OF THYMIC STROMAL LYMPHOPOIETIN (TSLP) GENOTYPES ON ASTHMA PHENOTYPES DEFINED BY THE ATOPY CLUSTER : INFLUENCE OF SMOKING HABITS

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  • Iijima Hiroaki
    Department of Respiratory Medicine, Tsukuba Medical Center
  • Yamada Hideyasu
    Department of Respiratory Medicine, Tsukuba Medical Center: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
  • Naito Takashi
    Department of Respiratory Medicine, Tsukuba Medical Center
  • Sakamoto Tohru
    Department of Pulmonary Medicine, University of Tsukuba
  • Masuko Hironori
    Department of Pulmonary Medicine, University of Tsukuba
  • Hirota Tomomitsu
    Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medicine Sciences, RIKEN
  • Tamari Mayumi
    Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medicine Sciences, RIKEN
  • Konno Satoshi
    First Department of Medicine, School of Medicine, Hokkaido University
  • Nishimura Masaharu
    First Department of Medicine, School of Medicine, Hokkaido University
  • Hizawa Nobuyuki
    Department of Pulmonary Medicine, University of Tsukuba

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Other Title
  • アレルゲン特異的IgE反応性から分類した喘息フェノタイプ : Thymic stromal lymphopoietin (TSLP)遺伝子と喫煙の役割
  • アレルゲン トクイテキ IgE ハンノウセイ カラ ブンルイ シタ ゼンソク フェノタイプ : Thymic stromal lymphopoietin(TSLP)イデンシ ト キツエン ノ ヤクワリ

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Abstract

Introduction: We have previously reported that a distinct sensitization pattern was associated with thymic stromal lymphopoietin (TSLP) genotype. The aim of this study is to identify the characteristics of asthma phenotypes determined by a cluster analysis of IgE responsiveness and the relationship between these phenotypes and TSLP genotypes. Patients and methods: We studied 297 patients of adult asthma and 1571 non-asthmatic healthy adults from Ibaraki, a prefecture in central Japan and Kamishihoro, a cedar-free, birch-dominant town in northern Japan. Levels of total serum IgE and specific IgE antibodies towards 14 major inhaled allergens were measured. With the use of these measures, cluster analysis was applied to classify the phenotypes of adult asthma. We also examined the genetic effects of 2 TSLP functional single nucleotide polymorphism (SNPs) on the development of each asthma phenotype using multinomial logistic regression analysis. Results: The cluster analysis identified four distinct clinical phenotypes of asthma, including "Dust mite dominant" (A, N=82), "Multiple pollen" (B, N=14), "Cedar dominant" (C, N=44), and "Low reactivity" (D, N=154). Asthma phenotype A consisted of younger patients with elevated IgE levels and decreased pulmonary function. Asthma phenotype B was characterized by sensitization by many pollen allergens. Asthma phenotype C was not formed in Kamishihoro. Asthma phenotype D was a group of older women who are less atopic. In current or past smokers, both TSLP SNPs (rs2289276 and rs3860933) were associated with the asthma phenotype D (odds ratio 2.11 [1.36-3.30] and 2.11 [1.34-3.33], respectively). Conclusion: In patients with adult asthma who are less atopic, the genetic polymorphisms of TSLP may have some important roles in the development of the disease in smokers.

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