Extracellular superoxide dismutase haplotypes are associated with acute lung injury and mortality.

Published

Journal Article

RATIONALE: Extracellular superoxide dismutase (EC-SOD) is a potent antioxidant that plays an important role in controlling oxidant-mediated stress and inflammation. High levels of EC-SOD are found in the lung. Acute lung injury (ALI) frequently occurs in patients with infection, and levels of EC-SOD have been shown to modulate severity of lung injury in transgenic animal models of endotoxemia-induced ALI. An R213G single nucleotide polymorphism (SNP) has been shown to alter levels of EC-SOD and patient outcomes in chronic obstructive pulmonary disease (COPD) and ischemic heart disease. OBJECTIVES: To determine genetic variation in the promoter and EC-SOD gene and to examine whether EC-SOD haplotype blocks are associated with clinical outcomes. METHODS: We sequenced the EC-SOD promoter and gene to determine genetic variation and linkage disequilibrium (LD) patterns in a European American population. Two separate patient populations with infection-associated ALI were also evaluated to determine whether EC-SOD haplotypes were associated with clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Sequencing resulted in the identification of 28 SNPs with relatively strong LD and 1 block consisting of 4691-5321-5360-5955-5982. This specific block was shown to be protective in two separate patient populations with infection associated ALI. In particular, patients with a GCCT haplotype had a reduced risk of time on the ventilator and mortality. CONCLUSIONS: These results indicate that a GCCT haplotype may reduce inflammation in the lung, thereby decreasing the severity of lung injury and ultimately protecting patients from mortality associated with infection-induced ALI.

Full Text

Duke Authors

Cited Authors

  • Arcaroli, JJ; Hokanson, JE; Abraham, E; Geraci, M; Murphy, JR; Bowler, RP; Dinarello, CA; Silveira, L; Sankoff, J; Heyland, D; Wischmeyer, P; Crapo, JD

Published Date

  • January 15, 2009

Published In

Volume / Issue

  • 179 / 2

Start / End Page

  • 105 - 112

PubMed ID

  • 18948423

Pubmed Central ID

  • 18948423

Electronic International Standard Serial Number (EISSN)

  • 1535-4970

Digital Object Identifier (DOI)

  • 10.1164/rccm.200710-1566OC

Language

  • eng

Conference Location

  • United States