title: Antioxidant response genes sequence variants and BPD susceptibility in VLBW infants.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, Wisconsin.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Sampath
authors.affiliation: Department of Pediatrics, Wheaton Franciscan Health Care, Milwaukee, Wisconsin.
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Garland
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, Wisconsin.
authors.forename: Daniel
authors.initials: D
authors.lastname: Helbling
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, Wisconsin.
authors.forename: David
authors.initials: D
authors.lastname: Dimmock
authors.affiliation: Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Mulrooney
authors.affiliation: Department of Pediatrics and Quantitative Health Sciences, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Pippa M
authors.initials: PM
authors.lastname: Simpson
authors.affiliation: Department of Pediatrics, Iowa Children's Hospital, University of Iowa, Iowa City, Iowa.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.affiliation: Department of Pediatrics, Iowa Children's Hospital, University of Iowa, Iowa City, Iowa.
authors.forename: John M
authors.initials: JM
authors.lastname: Dagle
mesh_terms: D061745:Antioxidant Response Elements / Q000235:genetics*; D001997:Bronchopulmonary Dysplasia / Q000235:genetics*; D004790:Enzyme Induction / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D008957:Models, Genetic; D051267:NF-E2-Related Factor 2 / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human