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Maternal Nrf2 and gluthathione-S-transferase polymorphisms do not modify associations of prenatal tobacco smoke exposure with asthma and lung function in school-aged children


Background Maternal smoking during pregnancy has detrimental effects on the respiratory health of infants and children. Polymorphisms of antioxidant genes including glutathione-S-transferases (GSTs) have been proposed as candidates for asthma and reduced lung function in children.

Methods Women enrolled in the Avon Longitudinal Study of Parents and Children reported smoking habits during pregnancy. Asthma status in their children was established at age 7.5 years from parental reports and lung function was measured by spirometry at age 8.5 years. Maternal and child DNA were genotyped for deletions of GSTM1 and GSTT1 and functional polymorphisms of GSTP1 and Nrf2 genes. Associations of prenatal tobacco smoke exposure with asthma and lung function in children were stratified by maternal genotype.

Results In 6606 children, maternal smoking during pregnancy was negatively associated with maximal mid expiratory flow (FEF25-75) (−0.05 SD units, 95% CI −0.07 to −0.03, p<0.001). There was little evidence for interactions between maternal smoking and any maternal genotype considered on children's asthma or lung function. Maternal smoking was associated with reduced childhood FEF25-75 only in mother-child pairs (n=1227) with both copies of GSTM1 deleted (−0.08 SD units, 95% CI −0.14 to −0.02, p=0.01) or (n=2313) at least one copy of GSTT1 present (−0.05 SD units, 95% CI −0.09 to 0, p=0.03).

Conclusion This study confirms a detrimental effect of intrauterine tobacco smoke exposure on childhood lung function but no strong evidence of modification by maternal genotype for important antioxidant genes. Adverse effects of fetal exposure to tobacco smoke on the respiratory health of children may be mediated by pathways other than oxidative stress.

  • Asthma
  • child
  • lung function tests, passive smoking
  • Glutathione-S-Transferase (GSTM1
  • GSTP1
  • GSTT1)
  • Nuclear erythroid 2 p45-related factor 2 (Nrf2)
  • prenatal exposure
  • delayed effects
  • asthma epidemiology
  • asthma genetics
  • paediatric asthma
  • respiratory measurement
  • tobacco and the lung

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  • Funding The UK Medical Research Council, the Wellcome Trust and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children. This research was specifically funded by the British Lung Foundation. SOS is an Asthma UK Senior Research Fellow.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Avon Longitudinal Study of Parents and Children Ethics and Law Committee (IRB 00003312) and local research ethics committee, University Hospitals Bristol NHS Trust.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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