title: Genomic insights into acute inflammatory lung injury.
abstract: Acute lung injury (ALI) is a devastating syndrome (usually associated with sepsis) that represents a major healthcare burden in the United States. We have focused our studies on unraveling the genetic underpinnings of this syndrome utilizing a candidate gene approach to identify novel genes for ALI susceptibility. Two novel genes identified by this approach include pre-B cell colony-enhancing factor (PBEF) and the gene for myosin light chain kinase (MLCK). PBEF protein levels were elevated in human bronchoalveolar lavage and serum samples from patients with ALI, and DNA sequencing identified two single nucleotide polymorphisms in the PBEF promoter (T-1001G, C-1543T) that were overrepresented in patients with sepsis-induced ALI. More recently, we found MLCK single polymorphisms and haplotypes to be associated with human ALI with unique variants observed in African-Americans with ALI. Thus genomic and genetic approaches represent powerful strategies in the identification of novel candidate genes and potential targets for ALI therapies.
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA. jgarcia@medicine.bsd.uchicago.edu
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: Liliana
authors.initials: L
authors.lastname: Moreno Vinasco
mesh_terms: D001777:Blood Coagulation / Q000235:genetics; D002874:Chromosome Mapping; D017281:Cost of Illness; D016207:Cytokines / Q000235:genetics; D005260:Female; D023281:Genomics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000235:genetics; D054409:Nicotinamide Phosphoribosyltransferase; D011110:Polymorphism, Genetic; D012128:Respiratory Distress Syndrome / Q000191:economics / Q000453:epidemiology / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: D016207:Cytokines; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D009219:Myosin-Light-Chain Kinase