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Am J Physiol Lung Cell Mol Physiol (July 28, 2006). doi:10.1152/ajplung.00266.2006
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Submitted on July 15, 2006
Accepted on July 19, 2006

Genomic Insights into Acute Inflammatory Lung Injury

Joe G.N. Garcia1* and Liliana Moreno2

1 Pritzker School of Medicine, University of Chicago, CHICAGO, Illinois, United States
2 Pulmonary & Critical Care Medicine, University of Chicago, CHICAGO, Illinois, United States

* To whom correspondence should be addressed. E-mail: jgarcia{at}medicine.bsd.uchicago.edu.

Acute Lung Injury (ALI) is a devastating syndrome (usually associated with sepsis) which 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 PBEF (pre-B cell colony enhancing factor) and the gene for MLCK (myosin light chain kinase). PBEF protein levels were elevated in human BAL and serum samples from patients with ALI and DNA sequencing identified two single nucleotides polymorphisms in the PBEF promoter (T-1001G, C-1543T) which were over-represented in patients with sepsis-induced ALI. More recently, we found MLCK SNPs (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.




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