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 (FEF(25-75)) (-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 FEF(25-75) 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).


CONCLUSIONS
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.
Henderson
A J
AJ
Department of Community-based Medicine, University of Bristol, UK. a.j.henderson@bris.ac.uk
Newson
R B
RB
Rose-Zerilli
M
M
Ring
S M
SM
Holloway
J W
JW
Shaheen
S O
SO
D001249:Asthma / Q000196:embryology* / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D002648:Child; D004739:England / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008450:Maximal Midexpiratory Flow Rate; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D014028:Tobacco Smoke Pollution; D005982:Glutathione Transferase