Heme Oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome

Chau Chyun Sheu, Rihong Zhai, Zhaoxi Wang, Michelle N. Gong, Paula Tejera, Feng Chen, Li Su, B. Taylor Thompson, David C. Christiani

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Objective: Heme oxygenase-1 (HO-1) acts in cytoprotection against acute lung injury. The polymorphic (GT) n repeat in the HO-1 gene (HMOX1) promoter regulates HMOX1 expression. We investigated the associations of HMOX1 polymorphisms with acute respiratory distress syndrome (ARDS) risk and plasma HO-1 levels. Design: Unmatched, nested case-control study. Setting: Academic medical center. Patients: Consecutive patients with ARDS risk factors upon ICU admission were prospectively enrolled. Cases were 437 Caucasians who developed ARDS and controls were 1,014 Caucasians who did not. Measurements and results: We genotyped the (GT) n polymorphism and three tagging single nucleotide polymorphisms (tSNPs) in 1,451 patients, and measured the plasma HO-1 levels in 106 ARDS patients. We clustered the (GT) n repeats into: S-allele (<24 repeats), M-allele (24-30 repeats) and L-allele (≥31 repeats). We found that longer (GT) n repeats were associated with reduced ARDS risk (P trend = 0.004 for both alleles and genotypes), but no individual tSNP was associated with ARDS risk. HMOX1 haplotypes were significantly associated with ARDS risk (global test, P = 0.016), and the haplotype S-TAG was associated with increased ARDS risk (OR, 1.75; 95% CI, 1.15-2.68; P = 0.010). Intermediate-phenotype analysis showed longer (GT) n repeats were associated with higher plasma HO-1 levels (P trend = 0.019 for alleles and 0.027 for genotypes). Conclusions: Longer (GT) n repeats in the HMOX1 promoter are associated with higher plasma HO-1 levels and reduced ARDS risk. The common haplotype S-TAG is associated with increased ARDS risk. Our results suggest that HMOX1 variation may modulate ARDS risk through the promoter microsatellite polymorphism.

Original languageEnglish (US)
Pages (from-to)1343-1351
Number of pages9
JournalIntensive Care Medicine
Volume35
Issue number8
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

Keywords

  • Acute respiratory distress syndrome
  • Genetic susceptibility
  • Haplotypes
  • Heme oxygenase-1
  • Microsatellite polymorphism
  • Molecular epidemiology

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'Heme Oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome'. Together they form a unique fingerprint.

  • Cite this