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

Pharmacogenet Genomics. 2009 Oct;19(10):790-9. doi: 10.1097/FPC.0b013e32833132b3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Feeding and Eating Disorders / genetics*
  • Female
  • Genetic Variation*
  • Humans
  • Male
  • Models, Biological
  • Pilot Projects
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin, 5-HT3 / genetics*
  • Receptors, Serotonin, 5-HT3 / metabolism

Substances

  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3