How the serotonin transporter gene (SLC6A4) shapes the phenotype in eating disorders: a role for genotype and promoter methylation

Introduction: The serotonergic system plays a role in the neurobiology of eating disorders. The serotonin transporter gene (SLC6A4) promoter polymorphism (5HTTLPR) was examined as a susceptibility gene for anorexia nervosa. DNA methylation of a CpG island upstream of the promoter region has been associated with childhood abuse and an interaction between 5HTTLPR genotype and methylation density was shown to predict unresolved loss or trauma. Methods: The aim of our study was to analyze 5HTTLPR genotype and SLC6A4 promoter methylation in a sample of in-patients with anorexia (n = 20) or bulimia nervosa (n = 22). Results: We found an effect of the 5HTTLPR on age of onset and on the Eating Disorder Inventory-2 subscales drive for thinness and body dissatisfaction. The methylation density of the 5‘ region of the promoter was associated with the BDI score and with binge eating behavior – the 3’ region was associated with purging and self-injuring behavior. In a general linear model computing several phenotypic characteristics as dependent and genotype and methylation as independent variables, whole model significance could be reached for BDI, self injuring behavior, age at onset, years of illness and drive for thinness. Conclusions: Our study shows that analysis of different regulatory mechanisms, i.e. genotype and promoter methylation together can help to explain phenotypic variability that could not be accounted for by one factor alone.