Thorax 65:897-902 doi:10.1136/thx.2009.125856
  • Asthma

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

  1. S O Shaheen2
  1. 1Department of Community-based Medicine, University of Bristol, UK
  2. 2Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College London, UK
  3. 3Respiratory Genetics Group, Division of Infection, Inflammation and Immunity and Division of Human Genetics, University of Southampton, UK
  4. 4Department of Social Medicine, University of Bristol, UK
  1. Correspondence to Henderson Alexander J, Community-based Medicine, University of Bristol, ALSPAC, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK; a.j.henderson{at}
  1. Contributors AJH and SOS conceived the study; RBN performed the statistical analyses; SMR, MR-Z and JWH conducted the genetic aspects of the study; SOS, AJH and JWH obtained the funding; all authors contributed to interpretation of the findings and writing the manuscript. AJH and SOS are guarantors for the contents of the paper.

  • Received 20 August 2009
  • Accepted 28 June 2010
  • Published Online First 30 August 2010


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.


  • 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.