title: AGER gene polymorphisms and soluble receptor for advanced glycation end product in patients with idiopathic pulmonary fibrosis.
abstract: The receptor for advanced glycation end product (RAGE) is a multiligand cell-surface receptor abundantly expressed in the lung. RAGE/ligand interaction has been postulated to participate in the pathogenesis of inflammatory diseases, while soluble RAGE (sRAGE) might act as a decoy receptor. A functional polymorphism rs2070600 in the gene coding RAGE (AGER) might modulate its receptor function. The aim of this study was to investigate the association of AGER polymorphisms and circulatory sRAGE with the development and progression of idiopathic pulmonary fibrosis (IPF).
  
  
  
  This study comprised 87 Japanese patients with IPF and 303 healthy controls. Seven tag polymorphisms in AGER were genotyped and their distributions were compared. We also measured serum sRAGE levels, and evaluated the correlations of sRAGE levels with AGER polymorphisms and the prognosis of the patients with IPF.
  
  
  
  The frequency of AGER rs2070600 genotype with minor allele was significantly higher in patients with IPF (OR = 1.84, 95% CI = 1.08-3.10). Additionally, the carriage of the rs2070600 minor allele and the presence of IPF were independently associated with reduced serum levels of sRAGE. Moreover, reduced sRAGE (≤471.8 pg/mL) was related to acute exacerbation of IPF and was an independent predictor of 5-year survival in patients with the disease (hazard ratio (HR) = 7.956, 95% CI = 1.575-53.34).
  
  
  
  These results suggest a possible association between a functional polymorphism in AGER and IPF disease susceptibility, and indicate a potential prognostic value of circulatory sRAGE.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kakuhiro
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Horimasu
authors.affiliation: Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ohshimo
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujitaka
authors.affiliation: Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Heart and Lung Centre, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Witold
authors.initials: W
authors.lastname: Mazur
authors.affiliation: Hiroshima Cosmopolitan University, Hiroshima, Japan.
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood* / Q000235:genetics
chemical_list: C000593871:AGER protein, human; D000067759:Receptor for Advanced Glycation End Products
keywords: genetic; interstitial lung disease; lung fibrosis; pulmonary fibrosis