Genetic polymorphisms of heme-oxygenase 1 (HO-1) may impact on acute kidney injury, bronchopulmonary dysplasia, and mortality in premature infants

Pediatr Res. 2015 Jun;77(6):793-8. doi: 10.1038/pr.2015.44. Epub 2015 Mar 9.

Abstract

Background: Heme oxygenase 1 (HO1) catalyzes heme degradation, and offers protection for several organs, including the kidney. Genetic polymorphisms of HO-1 are associated with poor clinical outcomes in several populations.

Population: We prospectively enrolled 117 premature infants (birth weight ≤1,200 g or postgestational age ≤31 wk) and evaluated two DNA genetic variants proximal to the promoter region of HO-1 (GT(n) repeats, and -413T>A SNP). We evaluated how these polymorphisms affect two clinical outcomes: (i) Acute Kidney Injury (AKI)-rise in serum creatinine (SCr) ≥ 0.3 mg/dl or ≥ 150-200% from lowest previous value, (ii) the composite of mortality and bronchopulmonary dysplasia (BPD) defined as receipt of oxygen at 36 wk postmenstrual age.

Results: AKI occurred in 34/117 (29%) of neonates; 12/117 (10%) died; 29/105 (28%) survivors had BPD. Neonates with TT genotype at 413T>A before the HO-1 promoter had higher rates of AKI (P < 0.05). There was no difference in number of GT(n) repeats and clinical outcomes.

Conclusion: We did not find an association between the GT(n) tandem repeat of HO-1 and AKI nor BPD/mortality. However, infants with TT genotype of the 413T>A genetic alteration had lower incidence of AKI. Further studies using larger cohorts are needed to better understand these relationships.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / genetics*
  • Bronchopulmonary Dysplasia / genetics*
  • DNA Primers / genetics
  • Heme Oxygenase-1 / genetics*
  • Humans
  • Infant
  • Infant Mortality
  • Infant, Newborn
  • Infant, Premature
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies
  • Ureohydrolases / blood

Substances

  • DNA Primers
  • Heme Oxygenase-1
  • Ureohydrolases
  • creatinase