Epigenetic Downregulation of Atrial Natriuretic Peptide but not Vasopressin mRNA Expression in Females with Eating Disorders is Related to Impulsivity

Abstract

Disturbances of volume-regulating mechanisms have already been implicated in the pathophysiology of eating disorders like anorexia or bulimia nervosa with the peptide hormones vasopressin and atrial natriuretic peptide (ANP) being of special interest. Aim of the present study was to investigate, whether the expression of the corresponding genes was altered and if so, if these changes could be explained by epigenetic mechanisms such as DNA methylation. We analyzed blood samples of 46 women suffering from anorexia (n ¼ 22) or bulimia nervosa (n ¼ 24) as well as of 30 healthy controls. Peripheral mRNA expression and DNA methylation of the vasopressin and the ANP precursor genes were assessed using real-time PCR. We found significantly lower levels of ANP mRNA in patients with eating disorders. This downregulation was accompanied by a hypermethylation of the ANP gene promoter in the bulimic subgroup. We did not find differences regarding expression or methylation of the vasopressin gene. ANP mRNA expression was inversely associated with impaired impulse regulation. We conclude that epigenetic mechanisms may contribute to the known alterations of ANP homeostasis in women with eating disorders.

Prospects for Epigenetic Epidemiology

“…The potential to identify distinct epigenetic biomarkers associated with eating disorders has also been explored (74,75). Disruption of epigenetic profile is also implicated in some adverse health outcomes for subjects conceived by means of assisted reproductive technologies (76).…”

Methylation of the glucocorticoid receptor gene promoter in bulimic women: Associations with borderline personality disorder, suicidality, and exposure to childhood abuse

“…Whether or not the preceding is true, evidence associates hypermethylation of various neuroregulatory genes with diverse mental-illness phenotypes, including suicidality, 18 borderline personality disorder (BPD), 20,21 and eating disorders (EDs). [22][23][24] The Present Study…”

Smoking, but Not Malnutrition, Influences Promoter-Specific DNA Methylation of the Proopiomelanocortin Gene in Patients with and without Anorexia Nervosa

“…50 In our previous studies (see Frieling et al 23,54,55 ), we observed aberrant methylation patterns for several genes of interest in patients with acute AN. In all cases, we found a significant hypermethylation of the gene promoters arguing also against a direct connection between the nutritional modulation of folate levels and gene-specific DNA methylation.…”