Polymorphisms in key pulmonary inflammatory pathways and the development of acute respiratory distress syndrome. (1st April 2015)

• Record Type: Journal Article
• Authors: Brown, Samuel M.; Grissom, Colin K.; Rondina, Matthew T.; Hoidal, John R.; Scholand, Mary Beth; Wolff, Roger K.; Morris, Alan H.; Paine, Robert
• Is Part Of: Experimental lung research. Volume 41:Number 3(2015:Mar.)
• Page Start: 155
• Page End: 162
• Publication Date: 2015-04-01
• Subjects: acute respiratory distress syndrome -- GM-CSF -- genetics -- RAGE; Lungs -- Periodicals; Lungs -- Diseases -- Periodicals; Lung Diseases; Lung -- physiology; Respiratory System; 616.24
• DOI: 10.3109/01902148.2014.983281
• Languages: English
• ISSNs: 0190-2148

Abstract

ABSTRACT: Purpose/Aim : Acute Respiratory Distress Syndrome (ARDS) is an important clinical and public health problem. Why some at-risk individuals develop ARDS and others do not is unclear but may be related to differences in inflammatory and cell signaling systems. The Receptor for Advanced Glycation Endproducts (RAGE) and Granulocyte-Monocyte Stimulating Factor (GM-CSF) pathways have recently been implicated in pulmonary pathophysiology; whether genetic variation within these pathways contributes to ARDS risk or outcome is unknown. Materials and Methods : We studied 842 patients from three centers in Utah and 14 non-Utah ARDS Network centers. We studied patients at risk for ARDS and patients with ARDS to determine whether Single Nucleotide Polymorphisms (SNPs) in the RAGE and GM-CSF pathways were associated with development of ARDS. We studied 29 SNPs in 5 genes within the two pathways and controlled for age, sepsis as ARDS risk factor, and severity of illness, while targeting a false discovery rate of ≤5%. In a secondary analysis we evaluated associations with mortality. Results : Of 842 patients, 690 had ARDS, and 152 were at-risk. Sepsis was the risk factor for ARDS in 250 (30%) patients. When controlling for age, APACHE III score, sepsis as risk factor, and multiple comparisons, no SNPs were significantly associated with ARDS. In a secondary analysis, only rs743564 in CSF2 approached significance with regard to mortality (OR 2.17, unadjusted p = 0.005, adjusted p = 0.15). Conclusions : Candidate SNPs within 5 genes in the RAGE and GM-CSF pathways were not significantly associated with development of ARDS in this multi-centric cohort.