title: Smoking, but not malnutrition, influences promoter-specific DNA methylation of the proopiomelanocortin gene in patients with and without anorexia nervosa.
abstract: OBJECTIVE
  Our pilot study evaluates the impact of environmental factors, such as nutrition and smoking status, on epigenetic patterns in a disease-associated gene.
  
  
  METHODS
  We measured the effects of malnutrition and cigarette smoking on proopiomelanocortin (POMC) promoter-specific DNA methylation in female patients with and without anorexia nervosa (AN). POMC and its derived peptides (alpha melanocyte stimulating hormone and adrenocorticotropic hormone) are implicated in stress and feeding response. Promoter-specific DNA methylation of the POMC gene was determined in peripheral blood mononuclear cells of 54 healthy female control subjects, 40 underweight patients with AN, and 21 weight-restored patients with AN using bisulfite sequencing. Malnutrition was characterized by plasma leptin.
  
  
  RESULTS
  POMC promoter-specific DNA methylation was not affected by diagnosis or nutritional status but significantly negatively associated with cigarette smoking.
  
  
  CONCLUSIONS
  Although malnutrition may be expected to reduce DNA methylation through its effects on one-carbon metabolism, our negative results are in line with several in vitro and clinical studies that did not show a direct relation between gene-specific DNA methylation and folate levels. In contrast, smoking has been repeatedly reported to alter DNA methylation of specific genes and should be controlled for in future epigenetic studies.
authors.affiliation: Dresden University of Technology, Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Dresden, Germany. stefan@nmr.mgh.harvard.edu
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
authors.forename: Esther
authors.initials: E
authors.lastname: Walton
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Roffman
authors.forename: Deike
authors.initials: D
authors.lastname: Weiss
authors.forename: Imke
authors.initials: I
authors.lastname: Puls
authors.forename: Nico
authors.initials: N
authors.lastname: Doehler
authors.forename: Roland
authors.initials: R
authors.lastname: Burghardt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lehmkuhl
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.forename: Marc
authors.initials: M
authors.lastname: Muschler
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
mesh_terms: D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood; D044342:Malnutrition / Q000097:blood / Q000235:genetics*; D010865:Pilot Projects; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000235:genetics*
chemical_list: D020738:Leptin; D011333:Pro-Opiomelanocortin