Venkatesh Sampath1, Jeffery S Garland2, Daniel Helbling1, David Dimmock1, Neil P Mulrooney3, Pippa M Simpson4, Jeffrey C Murray5, John M Dagle5. 1. Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital and Health Systems, Milwaukee, Wisconsin. 2. Department of Pediatrics, Wheaton Franciscan Health Care, Milwaukee, Wisconsin. 3. Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota. 4. Department of Pediatrics and Quantitative Health Sciences, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin. 5. Department of Pediatrics, Iowa Children's Hospital, University of Iowa, Iowa City, Iowa.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Jacqui M Marzec; Jason D Christie; Sekhar P Reddy; Anne E Jedlicka; Hue Vuong; Paul N Lanken; Richard Aplenc; Tae Yamamoto; Masayuki Yamamoto; Hye-Youn Cho; Steven R Kleeberger Journal: FASEB J Date: 2007-03-23 Impact factor: 5.191
Authors: P Zimniak; B Nanduri; S Pikuła; J Bandorowicz-Pikuła; S S Singhal; S K Srivastava; S Awasthi; Y C Awasthi Journal: Eur J Biochem Date: 1994-09-15
Authors: Jegen Kandasamy; Nelida Olave; Scott W Ballinger; Namasivayam Ambalavanan Journal: Am J Respir Crit Care Med Date: 2017-10-15 Impact factor: 21.405
Authors: Venkatesh Sampath; Daniel Helbling; Heather Menden; David Dimmock; Neil P Mulrooney; Jeffrey C Murray; John M Dagle; Jeffery S Garland Journal: J Pediatr Gastroenterol Nutr Date: 2016-03 Impact factor: 2.839