Association of C⁶⁰⁹T-Inborn Polymorphism of NAD(P)H: Quinone Oxidoreductase 1 with the Risk of Bronchopulmonary Dysplasia in Preterm Neonates

Abstract

Objectives In bronchopulmonary dysplasia (BPD), direct exposure to oxygen therapy can damage the pulmonary epithelium via oxidative stress. The NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme detoxifies genotoxic products of oxidative stress. The corresponding gene is subject to an inactivating single-nucleotide polymorphism (C⁶⁰⁹T), which reduces detoxifying ability. The aim of this study was to investigate whether the C⁶⁰⁹T NQO1 inborn gene polymorphism is associated with an increased risk of BPD.

Study Design Peripheral blood samples from 119 premature neonates ≤ 32 weeks of gestational age (42 BPD and 77 non-BPD) were used for DNA extraction. NQO1 genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method.

Results A significantly higher frequency of the NQO1 polymorphism was observed in BPD neonates compared with neonates without BPD. All neonates with ≤ 1,000 g birth weight who carried the mutant allele in heterozygous or homozygous state developed BPD. None of the BPD nonaffected group neonates with ≤ 1,000 g birth weight carried the NQO1 polymorphism.

Conclusion The higher incidence of NQO1 mutants among BPD neonates as well as the presence of the mutant allele in all neonates with ≤ 1,000 g who developed BPD provided the first evidence for a possible pathogenetic role of the C⁶⁰⁹T polymorphism in BPD susceptibility due to the reduction or loss of NQO1 enzymatic activity.

Keywords

bronchopulmonary dysplasia - NAD(P)H: quinone oxidoreductase 1 - single-nucleotide polymorphism - oxidative stress - neonatal chronic lung disease

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