Frieling Helge, Bleich Stefan, Otten Jeannette, Römer Konstanze D, Kornhuber Johannes, de Zwaan Martina, Jacoby Georg E, Wilhelm Julia, Hillemacher Thomas
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Neuropsychopharmacology. 2008 Oct;33(11):2605-9. doi: 10.1038/sj.npp.1301662. Epub 2008 Jan 2.
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=22) or bulimia nervosa (n=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.
容量调节机制紊乱已被认为与诸如神经性厌食症或神经性贪食症等饮食失调的病理生理学有关，其中肽类激素血管加压素和心钠素（ANP）备受关注。本研究的目的是调查相应基因的表达是否发生改变，如果发生改变，这些变化是否可以用DNA甲基化等表观遗传机制来解释。我们分析了46名患有神经性厌食症（n = 22）或神经性贪食症（n = 24）的女性以及30名健康对照者的血样。使用实时PCR评估血管加压素和ANP前体基因的外周mRNA表达和DNA甲基化。我们发现饮食失调患者的ANP mRNA水平显著降低。这种下调伴随着贪食症亚组中ANP基因启动子的高甲基化。我们未发现血管加压素基因在表达或甲基化方面存在差异。ANP mRNA表达与冲动调节受损呈负相关。我们得出结论，表观遗传机制可能导致饮食失调女性中已知的ANP稳态改变。
