Journal article
Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants
Pediatric research, Vol.77(3), pp.477-483
03/2015
DOI: 10.1038/pr.2014.200
PMCID: PMC4522928
PMID: 25518008
Abstract
Lung injury resulting from oxidative stress contributes to bronchopulmonary dysplasia (BPD) pathogenesis. Nuclear factor erythroid-2 related factor-2 (NFE2L2) regulates cytoprotective responses to oxidative stress by inducing enzymes containing antioxidant response elements (ARE). We hypothesized that ARE genetic variants will modulate susceptibility or severity of BPD in very-low-birth-weight (VLBW) infants.
Blood samples obtained from VLBW infants were used for genotyping variants in the SOD2, NFE2L2, GCLC, GSTP1, HMOX1, and NQO1 genes. SNPs were genotyped utilizing TaqMan probes (Applied Biosystems (ABI), Grand Island, NY), and data were analyzed using the ABI HT7900. Genetic dominance and recessive models were tested to determine associations between SNPs and BPD.
In our cohort (n = 659), 284 infants had BPD; 135 of whom developed severe BPD. Presence of the hypomorphic NQO1 SNP (rs1800566) in a homozygous state was associated with increased BPD, while presence of the NFE2L2 SNP (rs6721961) was associated with decreased severe BPD in the entire cohort and in Caucasian infants. In regression models that adjusted for epidemiological confounders, the NQO1 and the NFE2L2 SNPs were associated with BPD and severe BPD, respectively.
Genetic variants in NFE2L2-ARE axis may contribute to the variance in liability to BPD observed in preterm infants. These results require confirmation in independent cohorts.
Details
- Title: Subtitle
- Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants
- Creators
- Venkatesh Sampath - Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, WisconsinJeffery S Garland - Department of Pediatrics, Wheaton Franciscan Health Care, Milwaukee, WisconsinDaniel Helbling - Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, WisconsinDavid Dimmock - Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, WisconsinNeil P Mulrooney - Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, Minneapolis, MinnesotaPippa M Simpson - Department of Pediatrics and Quantitative Health Sciences, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WisconsinJeffrey C Murray - Department of Pediatrics, Iowa Children's Hospital, University of Iowa, Iowa City, IowaJohn M Dagle - Department of Pediatrics, Iowa Children's Hospital, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.77(3), pp.477-483
- DOI
- 10.1038/pr.2014.200
- PMID
- 25518008
- PMCID
- PMC4522928
- NLM abbreviation
- Pediatr Res
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Publisher
- United States
- Grant note
- R01 HD052953 / NICHD NIH HHS P30 ES004184 / NIEHS NIH HHS KL2 TR000056 / NCATS NIH HHS R01 HD057192 / NICHD NIH HHS ES004184 / NIEHS NIH HHS 8KL2TR000056 / NCATS NIH HHS UL1 TR000442 / NCATS NIH HHS
- Language
- English
- Date published
- 03/2015
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Biochemistry and Molecular Biology; Dental Research; Neonatology
- Record Identifier
- 9984025286102771
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