Endocrine Abstracts

Binge-eating disorder (BED) is characterized by recurrent (≥1 per week for 3 months), brief (≤2 h), psychologically distressing binge-eating episodes during which patients sense a lack of control and consume larger amounts of food than most people would under similar circumstances. The prevalence of BED is estimated to be between 2% and 3.5% and majority of individuals with BED are either overweight or obese. Most of the genetic research about eating disorders (ED) has focused on Anorexia Nervosa and Bulimia Nervosa; less data are available for BED due to its status as a newly recognized ED diagnosis. Although family and twin studies suggest the role of genetic factors in BED, candidate gene studies have not clearly confirmed the involvement of any one gene or genetic pathway. The aim of our study was to examine the existence of genetic variants associated with the onset of BED, using the Next-Generation (NGS) technology. We analyzed 42 genes involved in neuro-regulation of hunger/satiety associated with BMI and/or obesity and/or eating disorders in 50 obese patients (BMI >40 kg/m²) affected by BED and in a control population (72 normal weight subjects overlapping with our cases by sex and age without a diagnosis of eating disorders). Twenty-eight obese patients with BED are mutated in 19 of the genes analyzed; of these, 12% vs 4% of controls carries more than one variant in different genes. Within the control population, fewer mutations were found (33%) compared to the case population, in which the percentage of the changes (56%) was higher than the percentage of the Wild-Type (44%). These differences indicate a statistically significant enrichment of rare variants in BED patients compared to controls according to the Exact Fisher Test (P=0.0159). Several genes tested positive are known to be involved in the reward system and in the hedonic hunger (FTO, OPRM1, GHRL and LEPR), but we discovered new loci with a novel possible involvement in hedonic hunger. To date, our study is the first NGS study in a series of obese patients with BED and suggests for the first time some mechanisms potentially involved in conferring a genetic susceptibility to development of a BED.