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Updated: Jun 20, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Functional variants of the serotonin receptor type 3A and B gene are associated with eating disorders
Christian Hammer1, Johannes Kapeller, Max Endele
1Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld, Germany.
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.
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