title: Interaction between prenatal pesticide exposure and a common polymorphism in thePON1gene on DNA methylation in genes associated with cardio-metabolic disease risk-an exploratory study.
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 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,PON1Q192R 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 450 K methylation arrays.
  
  
  
  A specific methylation profile was observed in prenatally pesticide exposed children carrying thePON1192R-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 BMIZscore between birth and school age.
  
  
  
  DNA methylation may be an underlying mechanism explaining an adverse cardio-metabolic health profile in children carrying thePON1192R-allele and prenatally exposed to pesticides.
authors.affiliation: Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling (PPES), Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium.
authors.forename: Ken
authors.initials: K
authors.lastname: Declerck
authors.affiliation: Department of Epidemiology and Social Medicine, Antwerp University, Universiteitsplein 1, Antwerp, Belgium.|Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Remy
authors.affiliation: Department of Growth and Reproduction, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christine
authors.initials: C
authors.lastname: Wohlfahrt-Veje
authors.affiliation: Department of Growth and Reproduction, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.affiliation: Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.affiliation: Flemish Institute for Technological Research (VITO), Unit Environmental Risk and Health, Boeretang 200, Mol, Belgium.|Department of Biomedical Sciences, Antwerp University, Universiteitsplein 1, Antwerp, Belgium.|Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Greet
authors.initials: G
authors.lastname: Schoeters
authors.affiliation: Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling (PPES), Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Vanden Berghe
authors.affiliation: Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Helle R
authors.initials: HR
authors.lastname: Andersen
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics*; D002648:Child; D019175:DNA Methylation; D004198:Disease Susceptibility; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D024821:Metabolic Syndrome / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010575:Pesticides / Q000506:poisoning*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D010575:Pesticides; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Cardio-metabolic health; DNA methylation; Illumina 450 K methylation array; PON1 Q192R genotype; Paraoxonase 1; Prenatal pesticide exposure