title: Heme oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome.
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.
  
  
  METHODS
  Unmatched, nested case-control study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  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.
  
  
  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 (> or = 31 repeats). We found that longer (GT)n repeats were associated with reduced ARDS risk (Ptrend = 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 (Ptrend = 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.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Chau-Chyun
authors.initials: CC
authors.lastname: Sheu
authors.forename: Rihong
authors.initials: R
authors.lastname: Zhai
authors.forename: Zhaoxi
authors.initials: Z
authors.lastname: Wang
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Gong
authors.forename: Paula
authors.initials: P
authors.lastname: Tejera
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003422:Critical Care; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D051547:Heme Oxygenase-1 / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors
chemical_list: C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1