US EPA

3358673 

Journal Article 

Prenatal Air Pollution Exposures, DNA Methyl Transferase Genotypes, and Associations with Newborn LINE1 and Alu Methylation and Childhood Blood Pressure and Carotid Intima-Media Thickness in the Children's Health Study 

Breton, CV; Yao, J; Millstein, J; Gao, L; Siegmund, KD; Mack, W; Whitfield-Maxwell, L; Lurmann, F; Hodis, H; Avol, E; Gilliland, FD 

2016 

Yes 

Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 

124 

12 

1905-1912 

English 

27219456 

10.1289/EHP181 

WOS:000390211200018 

BACKGROUND: Although exposure to ambient air pollutants increases cardiovascular disease risk in adults little is known about the effects of prenatal exposure. Genetic variation and epigenetic alterations are two mechanisms that may influence the effects of early life exposures on cardiovascular phenotypes.

OBJECTIVES: We investigated whether genetic and epigenetic variation modify associations between prenatal air pollution on markers of cardiovascular risk in childhood.

METHODS: We used linear regression analysis to investigate the associations between prenatal pollutants (PM2.5, PM10, NO2, O3), Long Interspersed Nuclear Elements (LINE1) and AluYb8 DNA methylation levels measured in newborn bloodspots, and carotid intima-media thickness (CIMT) and blood pressure (BP) in 459 participants as part of the Children's Health Study. Interaction terms were also included to test for effect modification of these associations by genetic variation in methylation reprogramming genes.

RESULTS: Prenatal exposure to NO2 in the third trimester of pregnancy was associated with higher systolic BP in 11 year old children. Prenatal exposure to multiple air pollutants in the first trimester was associated with lower DNA methylation in LINE1 whereas later exposure to O3 was associated with higher LINE1 methylation levels in newborn bloodspots. The magnitude of associations with prenatal air pollution varied according to genotype for 11 SNPs within DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3 Beta (DNMT3B), Tet methylcytosine dioxygenase 2 (TET2), and Thymine DNA glycosylase (TDG) genes. While first trimester O3 exposure was not associated with CIMT and systolic BP overall, associations within strata of DNMT1or DNMT3b were observed and the magnitude and the direction of these associations depended on DNMT1 genotypes.

CONCLUSIONS: Genetic and epigenetic variation in DNA methylation reprogramming genes and in LINE1 retrotransposons may play important roles in downstream cardiovascular consequences of prenatal air pollution exposure.