Genomics

Dataset Information

46

Prenatal Pesticide Exposure Interacts with a Common Polymorphism in the PON1 Gene Leading to DNA Methylation Changes


ABSTRACT: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to a cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It has been hypothesized that epigenetics might be involved. The aim of the present study was to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children. Whole blood DNA methylation patterns in 48 children (6-11 years of age), whose mothers were occupationally unexposed or exposed to pesticides early in pregnancy, were determined by Illumina 450K methylation arrays. A specific methylation profile was observed in prenatally pesticide exposed children carrying the PON1 192R allele. Differentially methylated genes were enriched in several neuroendocrine signaling pathways including dopamine-DARPP32 feedback (appetite, reward pathways), corticotrophin releasing hormone signalling, nNOS, neuregulin signalling, mTOR signalling and type II diabetes mellitus signalling suggesting a possible link with the metabolic effects observed in these children. Furthermore, we were able to identify possible candidate genes which mediate the effect between pesticide exposure, leptin levels, delta BMI Z-score, and body fat percentage. In conclusion, DNA methylation may be an underlying mechanism explaining cardio-metabolic health outcomes in children that are prenatally exposed to pesticides and carrier of the PON1 192R allele. Overall design: Bisulfite converted DNA from whole blood of 48 children were hybridised to the Illumina Infinium HumanMethylation450 BeadChip. 25 children were prenatally exposed to pesticides of which 12 were carriers of the PON1 192R allele. 23 children were unexposed to pesticides of which 12 were carriers of the PON1 192R allele.

INSTRUMENT(S): Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)

SUBMITTER: Ken Declerck  

PROVIDER: GSE90117 | GEO | 2017-05-01

SECONDARY ACCESSION(S): PRJNA354431

REPOSITORIES: GEO

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Publications

Interaction between prenatal pesticide exposure and a common polymorphism in the <i>PON1</i> gene on DNA methylation in genes associated with cardio-metabolic disease risk-an exploratory study.

Declerck Ken K   Remy Sylvie S   Wohlfahrt-Veje Christine C   Main Katharina M KM   Van Camp Guy G   Schoeters Greet G   Vanden Berghe Wim W   Andersen Helle R HR  

Clinical epigenetics 20170405


<h4>Background</h4>Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (<i>PON1</i>) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA met  ...[more]

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