Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis.

Autor:	Manichaikul A; 1 Center for Public Health Genomics and.; 2 Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia., Sun L; 3 Department of Medicine, College of Physicians and Surgeons, and., Borczuk AC; 17 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York., Onengut-Gumuscu S; 1 Center for Public Health Genomics and., Farber EA; 1 Center for Public Health Genomics and., Mathai SK; 4 Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, New York., Zhang W; 5 Division of Pulmonary Sciences and Critical Care Medicine., Raghu G; 6 Department of Biostatistics and Informatics, Colorado School of Public Health, and., Kaufman JD; 16 Department of Medicine, University of Colorado Denver, Aurora, Colorado.; 7 Center for Interstitial Lung Disease.; 8 Department of Environmental and Occupational Health Sciences., Hinckley-Stukovsky KD; 9 Department of Medicine., Kawut SM; 10 Department of Epidemiology, and.; 11 Department of Biostatistics, University of Washington, Seattle, Washington., Jelic S; 3 Department of Medicine, College of Physicians and Surgeons, and., Liu W; 3 Department of Medicine, College of Physicians and Surgeons, and., Fingerlin TE; 12 Department of Medicine and.; 13 Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and., Schwartz DA; 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., Sell JL; 3 Department of Medicine, College of Physicians and Surgeons, and., Rich SS; 1 Center for Public Health Genomics and., Barr RG; 3 Department of Medicine, College of Physicians and Surgeons, and.; 15 Department of Biomedical Research, National Jewish Health, Denver, Colorado., Lederer DJ; 3 Department of Medicine, College of Physicians and Surgeons, and.; 15 Department of Biomedical Research, National Jewish Health, Denver, Colorado.
Jazyk:	angličtina
Zdroj:	Annals of the American Thoracic Society [Ann Am Thorac Soc] 2017 May; Vol. 14 (5), pp. 628-635.
DOI:	10.1513/AnnalsATS.201606-485OC
Abstrakt:	Rationale: 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. Objectives: 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.
Databáze:	MEDLINE
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