Transgenerational epigenetics: Maternal and grandmaternal gestational smoking influences DNA methylation of the AHRR gene

Introduction: Maternal (M) and grandmaternal (GM) gestational smoking increase the risk of wheeze in offspring. The aryl-hydrocarbon receptor repressor (AHRR) is involved in detoxification of tobacco smoke compounds. DNA methylation (DNA-M) at AHRR CpG site cg05575921 is lower on exposure to smoking. Aims: Proof-of-concept showing the role of DNA methylation in transgenerational effects of smoking. Effect of M and GM smoking on methlyation of AHRR cg05575921 in cord blood. Methods: The Isle of Wight birth cohort is an unselected birth cohort 1989-90 ( n =1456), children of the cohort were recruited in a third generation study. Smoking in pregnancy by M and GM during pregnancy was collected prospectively. The effect of gestational smoking on cg05575921 in F 2 cord blood ( n =96) was assessed by linear regression analysis. Results: DNA-M at cg05575921 was hypomethylated with either M or GM gestational smoking, though the effect of both M and GM smoking was greater. Infants exposed to both M and GM smoking had significantly lower cg05575921 methylation than unexposed infants (p= 0.002). Conclusion: Study shows that transgenerational gestational smoking influences cg05575921 methylation, the consequences of gestational smoking may compound across generations. Further studies are needed to confirm the role of epigenetics in transgenerational effects of environmental exposures.