학술논문
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.
Document Type
Article
Author
Source
Subject
*PRENATAL influences
*AIR pollution
*PRENATAL exposure delayed effects
*BLOOD pressure
*CARDIOVASCULAR diseases risk factors
*COMMUNITIES
*CONFIDENCE intervals
*GENETIC polymorphisms
*PASSIVE smoking
*PROBABILITY theory
*REGRESSION analysis
*RESEARCH
*RESEARCH funding
*SCHOOL children
*STATISTICS
*TRANSFERASES
*MATHEMATICAL variables
*DATA analysis
*DATA analysis software
*DNA methylation
*DESCRIPTIVE statistics
*CAROTID intima-media thickness
*EPIGENOMICS
*ODDS ratio
*GENOTYPES
*EVALUATION
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Language
ISSN
0091-6765
Abstract
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 (PM[sub 2.5], PM[sub 10], NO[sub 2], O[sub 3]), long interspersed nuclear elements (LINE1) and AluYb8 DNA methylation levels measured in newborn blood spot tests, 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 NO[sub 2] 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 O[sub 3] was associated with higher LINE1 methylation levels in newborn blood spots. The magnitude of associations with prenatal air pollution varied according to genotype for 11 SNPs within DNA methyltransferase 1 (DNMTI), DNA methyltransferase 3 Beta (DNMT3B), Tet methylcytosine dioxygenase 2 (TET2), and Thymine DNA glycosylase (TDG) genes. Although first-trimester O[sub 3] exposure was not associated with CIMT and systolic BP overall, associations within strata of DNMTI or DNMT3B were observed, and the magnitude and the direction of these associations depended on DNMTI 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. [ABSTRACT FROM AUTHOR]