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

Abstract

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 ) (À0.05 SD units, 95% CI À0.07 to À0.03, 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 (n¼1227) with both copies of GSTM1 deleted (À0.08 SD units, 95% CI À0.14 to À0.02, p¼0.01) or (n¼2313) at least one copy of GSTT1 present (À0.05 SD units, 95% CI À0.09 to 0, p¼0.03). 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.

Effects of in utero and Postnatal Exposure to Secondhand Smoke on Lung Function by Gender and Asthma Status: The Seven Northeastern Cities (SNEC) Study

“…Our findings on the effect of SHS exposure on lung function are consistent with the results of studies conducted in other countries and areas [9,[21][22][23][24][25][26][27][28][29] , which also provided evidence of an association between SHS exposure and respiratory outcomes. For example, a study in the US, conducted by the National Health and Nutrition Examination Survey, on children 4-16 years of age identified an association between current SHS and reduced lung function, although there was a different effect for different age groups [24] .…”

Epigenetic Control of Gene Expression in the Lung

“…Two subsequent independent epidemiological studies have demonstrated that in utero exposure to folate (a methylating agent) is associated with the risk of developing asthma in humans (51,52). In utero exposure to cigarette smoke is also associated with the development of asthma in children (55,56), and given the recent evidence for modulation of epigenetic marks by cigarette smoke, it is possible that changes in DNA methylation or specific histone modifications mediate the effect of prenatal exposure to cigarette smoke on the development of allergic airway disease; no publications to date have demonstrated this link.…”

Quantitative Assessment of the Association Between the GSTM1-Null Genotype and the Risk of Childhood Asthma

“…One study contained four case-control studies from different ethnicities (Gilliland et al, 2002), and two studies contained two individual case-control studies, respectively (Kamada et al, 2007;Minelli et al, 2010). Finally, 19 casecontrol studies from 14 publications with 4,543 childhood asthma cases and 19,394 controls were included into this meta-analysis (Vavilin et al, 2000;Gilliland et al, 2002;Kabesch et al, 2004;Lee et al, 2005;Ercan et al, 2006;Hanene et al, 2007;Kamada et al, 2007;Li et al, 2009;Henderson et al, 2010;Lima et al, 2010;Minelli et al, 2010;Tung et al, 2011;Karam et al, 2012;Piacentini et al, 2012). Among those 19 case-control studies, 8 (75.0%) were from Caucasian populations, and 6 (12.5%) were from Asians and 3 from Africans (Table 1).…”