Gavrili Stavroula, Zachaki Sophia, Daraki Aggeliki, Polycarpou Elena, Manola Kalliopi, Stavropoulou Chryssa, Sambani Constantina, Baroutis George
Neonatal Intensive Care Unit, General District Hospital Athens "Alexandra," Athens, Greece.
Laboratory of Health Physics, Radiobiology and Cytogenetics, National Center of Scientific Research (NCSR) "Demokritos," Athens, Greece.
Am J Perinatol. 2016 May;33(6):535-9. doi: 10.1055/s-0035-1569991. Epub 2015 Dec 18.
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 (C(609)T), which reduces detoxifying ability. The aim of this study was to investigate whether the C(609)T 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 C(609)T polymorphism in BPD susceptibility due to the reduction or loss of NQO1 enzymatic activity.
目的 在支气管肺发育不良（BPD）中，直接接受氧疗可通过氧化应激损伤肺上皮细胞。烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）：醌氧化还原酶1（NQO1）可使氧化应激产生的基因毒性产物解毒。相应基因存在一种失活的单核苷酸多态性（C(609)T），可降低解毒能力。本研究旨在调查C(609)T NQO1先天性基因多态性是否与BPD风险增加有关。研究设计 采集119例胎龄≤32周的早产儿（42例BPD患儿和77例非BPD患儿）的外周血样本用于DNA提取。采用聚合酶链反应-限制性片段长度多态性方法进行NQO1基因分型。结果 与无BPD的新生儿相比，BPD新生儿中NQO1多态性的频率显著更高。所有出生体重≤1000g且携带杂合或纯合突变等位基因的新生儿均发生了BPD。出生体重≤1000g的BPD未受累组新生儿均未携带NQO1多态性。结论 BPD新生儿中NQO1突变体的发生率较高，以及所有出生体重≤1000g且发生BPD的新生儿中均存在突变等位基因，这首次为C(609)T多态性因NQO1酶活性降低或丧失而在BPD易感性中可能发挥的致病作用提供了证据。
