Implication of genetic and epigenetic variations of bdnf gene in anorexia nervosa

Anorexia nervosa (AN) is a chronic psychiatric disorder resulting from abnormal eating habits. AN involves genetic and epigenetic factors supporting that AN is a metabo-psychiatric disorder. Brain-derived neurotrophic factor (BDNF) gene is associated with AN. BDNF modulates the central control of food intake and its injection induces weight loss and anorexia. Genetic association of variant rs6265-Val66Met and electrodermal response to images of thinness supports a reward effect of weight loss in AN. The aim of our work is to investigate the impact of rs6265 genetic variant and epigenetic modifications of DNA methylation level among BDNF gene and consequences on BDNF level concentrations in patients suffering of AN. Genomic DNA was isolated from 24 patients suffering of AN and 48 controls. DNA methylation was measured for CpG sites spanning the BDNF gene using Infinium HumanMethylation450 BeadChip technology. The genotyping of rs6265 was performed by Taqman-SNP assay. The BDNF concentration was measured by ELISA from plasmas of subjects. Statistical comparisons were performed between groups of patients and controls for the genetics, DNA methylation and BDNF level, as well as according to the rs6265 risk allele. We observe that several CpG sites are significantly hypomethylated in patients suffering of AN compared to controls. Furthermore, patients suffering of AN show statistical significantly higher BDNF concentration levels than controls. Finally, this BDNF concentration is significantly higher in AN carrying the risk Met66 allele. This work demonstrates genetic and epigenetic effects of BDNF, which could constitute relevant diagnostic biomarkers of AN, and their likely consequences in the pathophysiology of AN. Other neurotrophin's genes could be also involved in the AN. Furthermore, the investigation of these BDNF biomarkers, and other neurotrophins, could be also helpful to prognostic the AN patients that will evolve to the remission.