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


METHODS



METHODS
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.


CONCLUSIONS
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.
Divisions of Pediatric Nephrology and Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
David J
DJ
Askenazi
Divisions of Pediatric Nephrology and Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Brian
B
Halloran
Divisions of Pediatric Nephrology and Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Neha
N
Patil
Divisions of Pediatric Nephrology and Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Susan
S
Keeling
Divisions of Pediatric Nephrology and Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Behtash
B
Saeidi
Divisions of Pediatric Nephrology and Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Rajesh
R
Koralkar
Divisions of Pediatric Nephrology and Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Namasivayam
0000000307319092
N
Ambalavanan
D058186:Acute Kidney Injury / Q000235:genetics*; D001997:Bronchopulmonary Dysplasia / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D007234:Infant, Premature; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D014512:Ureohydrolases / Q000097:blood
D017931:DNA Primers; D051547:Heme Oxygenase-1; D014512:Ureohydrolases; C019944:creatinase