OXTR DNA methylation differentiates men on the obesity spectrum with and without binge eating disorder.

Background: The neuropeptide oxytocin (OXT) plays a role in the regulation of eating behavior and metabolism. OXT functioning is altered in patients with eating and weight disorders, and a variant of the oxytocin receptor gene (OXTR) has been associated with impulsive eating behavior as it is seen in patients with binge eating disorder (BED). Gene × environment interactions could play a role in BED. One mechanism mediating this interaction is the epigenetic alteration of gene expression. We therefore investigated if DNA methylation of the OXTR differs between individuals with obesity depending on a comorbid BED. We analyzed DNA methylation of the OXTR in peripheral blood of 227 individuals on the obesity spectrum (mean age: 40.3 ± 13.1 yrs; mean BMI: 38.6 ± 7.3 kg/m), 130 of which were diagnosed with BED.

Results: There were no overall differences in OXTR methylation between participants with and those without BED (p > 0.05), while both subgroups were comparable regarding age and body mass index (BMI), but significantly differed in sex distribution (p = 0.035). We found no relationship between mean DNA methylation and BMI or self-reported eating disorder (ED) pathology. Analyzing potential sex differences revealed a significantly lower OXTR DNA methylation in male participants with BED as compared to those without BED (p = 0.017). No such difference was found in the female subsample (p > 0.05).

Conclusions: Clinically significant binge eating pathology might be associated with lower OXTR DNA methylation exclusively in males. The differential DNA methylation of OXTR in males with BED supports the view that BED represents a phenotype within the obesity spectrum that is characterized by specific vulnerability factors. A better understanding of the epigenetic underpinnings of the OXT system might contribute to the refinement of OXT administration approaches as potential interventions in eating and weight disorders.