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

TY - JOUR

T1 - Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk

T2 - an exploratory study

AU - Declerck, Ken

AU - Remy, Sylvie

AU - Wohlfahrt-Veje, Christine

AU - Main, Katharina M

AU - Van Camp, Guy

AU - Schoeters, Greet

AU - Vanden Berghe, Wim

AU - Andersen, Helle R

PY - 2017/4/5

Y1 - 2017/4/5

N2 - BACKGROUND: 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 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 methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children.METHODS: 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 450 K methylation arrays.RESULTS: 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 signaling, nNOS, neuregulin signaling, mTOR signaling, and type II diabetes mellitus signaling. Furthermore, we were able to identify possible candidate genes which mediated the associations between pesticide exposure and increased leptin level, body fat percentage, and difference in BMI Z score between birth and school age.CONCLUSIONS: DNA methylation may be an underlying mechanism explaining an adverse cardio-metabolic health profile in children carrying the PON1 192R-allele and prenatally exposed to pesticides.

AB - BACKGROUND: 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 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 methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children.METHODS: 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 450 K methylation arrays.RESULTS: 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 signaling, nNOS, neuregulin signaling, mTOR signaling, and type II diabetes mellitus signaling. Furthermore, we were able to identify possible candidate genes which mediated the associations between pesticide exposure and increased leptin level, body fat percentage, and difference in BMI Z score between birth and school age.CONCLUSIONS: DNA methylation may be an underlying mechanism explaining an adverse cardio-metabolic health profile in children carrying the PON1 192R-allele and prenatally exposed to pesticides.

KW - Aryldialkylphosphatase/genetics

KW - Child

KW - DNA Methylation

KW - Disease Susceptibility

KW - Female

KW - Gene-Environment Interaction

KW - Genotype

KW - Humans

KW - Male

KW - Maternal Exposure/adverse effects

KW - Metabolic Syndrome/genetics

KW - Oligonucleotide Array Sequence Analysis

KW - Pesticides/poisoning

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/genetics

KW - Prospective Studies

U2 - 10.1186/s13148-017-0336-4

DO - 10.1186/s13148-017-0336-4

M3 - Journal article

C2 - 28396702

SN - 1868-7075

VL - 9

JO - Clinical Epigenetics

JF - Clinical Epigenetics

M1 - 35

ER -