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. Method: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. W W WObjectif : Notre étude pilote évalue l'effet des facteurs environnementaux, comme la nutrition et le statut de fumeur, sur les modèles épigénétiques d'un gène associé à la maladie.Méthode : Nous avons mesuré les effets de la malnutrition et du tabagisme sur la méthylation de l'ADN spécifique au promoteur du gène pro-opiomélanocortin (POMC) chez des patientes avec et sans anorexie mentale (AM). Le POMC et ses peptides dérivés (hormone mélanostimulante alpha et hormone adrénocorticotrope) sont impliqués dans la

Epigenetic Signaling in Psychiatric Disorders

“…Among weight-restored anorexic patients, smoking (but not malnutrition) was associated with decreased POMC promoter methylation within peripheral monocytes 187 . However, the degree to which this is relevant for POMC expression or epigenetic regulation within the brain is unknown.…”

Dietary Flavanols Modulate the Transcription of Genes Associated with Cardiovascular Pathology without Changes in Their DNA Methylation State

“…compared to lifespan) intervention studies [50], [51], [52]. In addition to smoking, age or clinical parameters (blood pressure, pulse, LDL/HDL ratio, plasma CRP, BMI, serum cholesterol) may introduce variation in genome-wide DNA methylation patterns [50], [51], [52], [53], [54], [55], [56], [57], [58], [59]. Considering the stochastic nature of DNA methylation changes, we cannot exclude that a relative short diet intervention (8 weeks) is not sufficient to trigger a 10% change in DNA methylation (our cut-off criterion for differential methylation) as compared to DNA methylation changes following many years (>15 y) of heavy smoking, hypertension and/or aging.…”

Genetics and epigenetics of eating disorders

“…Expression of the functionally relevant long POMC mRNA was linked to leptin levels in 31 individuals with acute AN. 216 In a different study by the same group of researchers, no association between BMI or AN status (acute versus weight recovered) and POMC promoter methylation was observed, but hypomethylation was associated with cigarette smoking, 217 suggesting a possible role for environmental factors rather than AN diagnosis in POMC expression.…”