title: [Effects of thymic stromal lymphopoietin (TSLP) genotypes on asthma phenotypes defined by the atopy cluster -influence of smoking habits-].
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, Tsukuba Medical Center.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Department of Respiratory Medicine, Tsukuba Medical Center; Department of Pulmonary Medicine, University of Tsukuba.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Pulmonary Medicine, University of Tsukuba.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yatagai
authors.affiliation: Department of Pulmonary Medicine, University of Tsukuba.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Respiratory Medicine, Tsukuba Medical Center.
authors.forename: Takashi
authors.initials: T
authors.lastname: Naito
authors.affiliation: Department of Pulmonary Medicine, University of Tsukuba.
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Pulmonary Medicine, University of Tsukuba.
authors.forename: Hironori
authors.initials: H
authors.lastname: Masuko
authors.affiliation: Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medicine Sciences, RIKEN.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Laboratory for Respiratory and Allergic Diseases, Core for Genomic Medicine, Center for Integrative Medicine Sciences, RIKEN.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.affiliation: First Department of Medicine, School of Medicine, Hokkaido University.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Konno
authors.affiliation: First Department of Medicine, School of Medicine, Hokkaido University.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Pulmonary Medicine, University of Tsukuba.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000145:classification / Q000235:genetics* / Q000276:immunology; D016000:Cluster Analysis; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000145:classification / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics*; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D016207:Cytokines; D007073:Immunoglobulin E; D000094632:Thymic Stromal Lymphopoietin