Functional variants of the serotonin receptor type 3A and B gene are associated with eating disorders

Objective As a key player in modulating both human physiological and behavioural functions including anxiety, perception and in particular appetite, serotonin (5-hydroxytryptamine, 5-HT) is likely to be involved in the aetiology of eating disorders. Studies showing serotonin receptor type 3 (5-HT3) receptors to mediate food intake depression (anorexic response) have triggered our interest in investigating the putative role of variants in the 5-HT3 receptor genes, HTR3A and HTR3B, in the susceptibility to anorexia nervosa (AN) and bulimia nervosa (BN). Methods Two hundred and sixty-five patients with AN and 91 patients with BN as well as 191 healthy controls served as a pilot study group for mutational analysis by direct sequencing. Variants showing a significant association were subsequently genotyped in an independent Spanish cohort of 78 patients with AN and 119 patients with BN as well as 331 healthy controls for replication purposes. Results In the pilot study, we found the coding HTR3B variant, p.Y129S, (rs1176744, P=0.004, odds ratio=2.06) to be associated with the restrictive subtype of AN. The association was confirmed in the Spanish study group (P=0.034, odds ratio=2.26). Conclusion Our study provides first evidence for an involvement of 5-HT3 variants in the aetiopathology of eating disorders in humans. Pharmacogenetics and Genomics 19:790-799 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.