title: Therapeutic implication of genetic variants of IL13 and STAT4 in airway remodelling with bronchial asthma.
abstract: Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched.
  
  
  
  We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS.
  
  
  
  In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high-dose ICSs administered to asthmatic patients who were homozygous for IL13 AA of rs20541 or STAT4 TT of rs925847 and who progressed to airway remodelling were investigated.
  
  
  
  High-dose ICS treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847. The increased concentrations of the mediators IL23, IL11, GMCSF, hyaluronic acid, IL24, and CCL8 in bronchial lavage fluid (BLF) were diminished after high-dose ICS treatment in patients homozygous for IL13 AA of rs20541.
  
  
  
  IL13 AA of rs20541 and STAT4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high-dose ICSs to asthmatic patients with genetic variants of IL13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT4 TT did not respond to high-dose ICSs. Therefore, using medications other than ICSs must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype-specific therapies for bronchial asthma.
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Horii
authors.affiliation: Department of Cardiovascular Surgery, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Tsuboi
authors.affiliation: Department of Medical Oncology, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Obara
authors.affiliation: Department of Thoracic Surgery, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanita
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kanno
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamauchi
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D056151:Airway Remodeling / Q000187:drug effects / Q000235:genetics*; D000483:Alleles; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050797:STAT4 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D016207:Cytokines; D018793:Interleukin-13; D050797:STAT4 Transcription Factor; D007073:Immunoglobulin E
keywords: IL13; STAT4; airway remodelling; asthma; bronchial biopsy; genetic variation; single nucleotide polymorphisms