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: Population: We prospectively enrolled 117 premature infants (birth weight ≤1200 gm. or post gestational age ≤31 weeks) and evaluated 2 DNA genetic variants proximal to the promoter region of HO-1 (GT(n) repeats, and–413T>A SNP). We evaluated how these polymorphisms affect 2 clinical outcomes i) AKI - rise in serum creatinine (SCr) ≥ 0.3 mg/dl or ≥ 150–200% from lowest previous value, ii) bronchopulmonary dysplasia (BPD) defined as receipt of oxygen at 36 weeks post menstrual age (PMA) / mortality. 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 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.