title: Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis.
abstract: BACKGROUND
  The receptor for advanced glycation end products (RAGE) is underexpressed in idiopathic pulmonary fibrosis (IPF) lung, but the role of RAGE in human lung fibrosis remains uncertain.
  
  
  OBJECTIVE
  To examine (1) the association between IPF risk and variation at rs2070600, a functional missense variant in AGER (the gene that codes for RAGE), and (2) the associations between plasma-soluble RAGE (sRAGE) levels with disease severity and time to death or lung transplant in IPF.
  
  
  METHODS
  We genotyped the rs2070600 single-nucleotide polymorphism in 108 adults with IPF and 324 race-/ethnicity-matched control subjects. We measured plasma sRAGE by ELISA in 103 adults with IPF. We used generalized linear and additive models as well as Cox models to control for potential confounders. We repeated our analyses in 168 (genetic analyses) and 177 (sRAGE analyses) adults with other forms of interstitial lung disease (ILD).
  
  
  RESULTS
  There was no association between rs2070600 variation among adults with IPF (P = 0.31). Plasma sRAGE levels were lower among adults with IPF and other forms of ILD than in control subjects (P < 0.001). The rs2070600 allele A was associated with a 49% lower sRAGE level (95% confidence interval [CI], 11 to 71%; P = 0.02) among adults with IPF. In adjusted analyses, lower sRAGE levels were associated with greater disease severity (14% sRAGE decrement per 10% FVC decrement; 95% CI, 5 to 22%) and a higher rate of death or lung transplant at 1 year (adjusted hazard ratio, 1.9 per logarithmic unit of sRAGE decrement; 95% CI, 1.2-3.3) in IPF. Similar findings were observed in a heterogeneous group of adults with other forms of ILD.
  
  
  CONCLUSIONS
  Lower plasma sRAGE levels may be a biological measure of disease severity in IPF. Variation at the rs2070600 single-nucleotide polymorphism was not associated with IPF risk.
authors.affiliation: 1 Center for Public Health Genomics and.|2 Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.affiliation: 3 Department of Medicine, College of Physicians and Surgeons, and.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: 17 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Borczuk
authors.affiliation: 1 Center for Public Health Genomics and.
authors.forename: Suna
authors.initials: S
authors.lastname: Onengut-Gumuscu
authors.affiliation: 1 Center for Public Health Genomics and.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Farber
authors.affiliation: 4 Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, New York.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Mathai
authors.affiliation: 5 Division of Pulmonary Sciences and Critical Care Medicine.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 6 Department of Biostatistics and Informatics, Colorado School of Public Health, and.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Raghu
authors.affiliation: 16 Department of Medicine, University of Colorado Denver, Aurora, Colorado.|7 Center for Interstitial Lung Disease.|8 Department of Environmental and Occupational Health Sciences.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kaufman
authors.affiliation: 9 Department of Medicine.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Hinckley-Stukovsky
authors.affiliation: 10 Department of Epidemiology, and.|11 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.affiliation: 3 Department of Medicine, College of Physicians and Surgeons, and.
authors.forename: Sanja
authors.initials: S
authors.lastname: Jelic
authors.affiliation: 3 Department of Medicine, College of Physicians and Surgeons, and.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: 12 Department of Medicine and.|13 Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.affiliation: 4 Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, New York.|12 Department of Medicine and.|13 Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.|14 Center for Genes, Environment and Health and.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.affiliation: 3 Department of Medicine, College of Physicians and Surgeons, and.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sell
authors.affiliation: 1 Center for Public Health Genomics and.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: 3 Department of Medicine, College of Physicians and Surgeons, and.|15 Department of Biomedical Research, National Jewish Health, Denver, Colorado.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.affiliation: 3 Department of Medicine, College of Physicians and Surgeons, and.|15 Department of Biomedical Research, National Jewish Health, Denver, Colorado.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood* / Q000235:genetics*; D012995:Solubility; D014481:United States
chemical_list: D000067759:Receptor for Advanced Glycation End Products
keywords: biomarker; interstitial lung disease; pulmonary fibrosis