title: Prenatal exposure to cigarette smoke interacts with OPRM1 to modulate dietary preference for fat.
abstract: BACKGROUND
  Preference for fatty foods is a risk factor for obesity. It is a complex behaviour that involves the brain reward system and is regulated by genetic and environmental factors, such as the opioid receptor mu-1 gene (OPRM1) and prenatal exposure to maternal cigarette smoking (PEMCS). We examined whether OPRM1 and PEMCS interact in influencing fat intake and whether exposure-associated epigenetic modifications of OPRM1 may mediate this gene-environment interaction.
  
  
  METHODS
  We studied adolescents from a French Canadian genetic founder population, half of whom were exposed prenatally to maternal cigarette smoking. Fat intake was assessed with a 24-hour food recall in the form of a structured interview conducted by a trained nutritionist. The OPRM1 variant rs2281617 was genotyped for the whole sample with the Illumina Human610-Quad and HumanOmniExpress BeadChips. Methylation of blood DNA was assessed at 21 CpGs across OPRM1 in a subset of the sample using the Illumina HumanMethylation450 BeadChip.
  
  
  RESULTS
  We included 956 adolescents in our study. In the whole sample, OPRM1 (T carrier in rs2281617) was associated with lower fat intake (-1.6%, p = 0.017), and PEMCS was associated with higher fat intake (+1.6%, p = 0.005). OPRM1 and PEMCS interacted with each other (p = 0.003); the "protective" (fat intake-lowering) allele of OPRM1 was associated with lower fat intake in nonexposed (-3.2%, p < 0.001) but not in exposed individuals (+0.8%, p = 0.42). Further, PEMCS was associated with lower DNA methylation across multiple CpGs across OPRM1 in exposed versus nonexposed individuals (p = 0.031).
  
  
  CONCLUSIONS
  A limitation of our study was its cross-sectional design.
  
  
  CONCLUSIONS
  Our study suggests that PEMCS may interact with OPRM1 in increasing fat preference. Silencing of the protective OPRM1 allele in exposed adolescents might be related to epigenetic modification of this gene.
authors.affiliation: Hospital for Sick Children, University of Toronto, Toronto, Ont.
authors.forename: Ken W K
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Que.
authors.forename: Michal
authors.initials: M
authors.lastname: Abrahamowicz
authors.affiliation: Montreal Neurological Institute, McGill University, Montréal, Que.
authors.forename: Gabriel T
authors.initials: GT
authors.lastname: Leonard
authors.affiliation: Department of Psychology, Université du Québec à Chicoutimi, Chicoutimi, Que.
authors.forename: Louis
authors.initials: L
authors.lastname: Richer
authors.affiliation: ÉCOBES, Recherche et transfert, Cégep de Jonquière, Jonquière, Que.; Department of Human Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que.
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.affiliation: ÉCOBES, Recherche et transfert, Cégep de Jonquière, Jonquière, Que.; Department of Human Sciences, Université du Québec à Chicoutimi, Chicoutimi, Que.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Veillette
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Reischl
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Que.; ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Chicoutimi, Que.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
authors.affiliation: ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Chicoutimi, Que.; Community Genomic Centre, Université de Montréal, Chicoutimi Hospital, Chicoutimi, Que.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Ont., Canada.
authors.forename: Tomas
authors.initials: T
authors.lastname: Paus
authors.affiliation: Hospital for Sick Children, University of Toronto, Toronto, Ont.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
mesh_terms: D000293:Adolescent; D002170:Canada; D018899:CpG Islands; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004041:Dietary Fats; D005260:Female; D005518:Food Preferences / Q000502:physiology*; D059647:Gene-Environment Interaction; D060005:Genotyping Techniques; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D044465:White People / Q000235:genetics
chemical_list: D004041:Dietary Fats; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu