title: Effect of genetic variation of IL-13 on airway remodeling in bronchial asthma.
abstract: BACKGROUND
  IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation, and common single-nucleotide polymorphisms in IL13 are associated with allergic phenotypes in several ethnically diverse populations. In particular, IL13Q110 is the non-conservative replacement of a positively charged arginine (R) with a neutral glutamine (Q) at position 110 of IL-13, and as we already know, individuals homozygous for glutamine (Q110/Q110) are strongly associated with asthma and IgE. IL13Q110 has been demonstrated to show that increased allergic inflammation depended on the enhanced IL-13-mediated Th2 effector function. Therefore, we investigated whether Q110/Q110 accelerated the decline in pulmonary function and development of airway remodeling of asthmatic patients in the general population.
  
  
  METHODS
  A total 336 asthmatic subjects living in Japan were recruited, genotyped, and had a pulmonary function test performed on them. To analyze airway inflammation and remodeling, bronchial lavage fluid (BLF) and endobronchial biopsy specimens were examined.
  
  
  RESULTS
  Forced expiratory volume in one second (FEV1), %predicted, forced expiratory volume/forced vital capacity ratio, and forced expiratory flow 25-75%, % predicted were significantly decreased in Q110/Q110 compared to R110/R110, and the decline in FEV1 was increased significantly in Q110/Q110 compared to R110/R110. The concentration of IL-13, IL-23, IL-11, GM-CSF, hyaluronic acid, and CCL8 in BLF were increased in Q110/Q110 compared to R110/R110 and the thickness of the subepithelial layer was thicker.
  
  
  CONCLUSIONS
  Our study demonstrates that Q110/Q110 increases, at least in part, allergic inflammation and the propensity for airway remodeling, thus resulting in low lung function.
authors: Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Japan.
authors: Hiromi
authors: H
authors: Nagashima
authors: Yutaka
authors: Y
authors: Nakamura
authors: Hiroyuki
authors: H
authors: Kanno
authors: Takashi
authors: T
authors: Sawai
authors: Hiroshi
authors: H
authors: Inoue
authors: Kohei
authors: K
authors: Yamauchi
mesh_terms: D000328:Adult; D000368:Aged; D056151:Airway Remodeling / Q000235:genetics*; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D018793:Interleukin-13