title: Functional variants of the serotonin receptor type 3A and B gene are associated with eating disorders.
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).
  
  
  CONCLUSIONS
  Our study provides first evidence for an involvement of 5-HT3 variants in the aetiopathology of eating disorders in humans.
authors.affiliation: Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hammer
authors.forename: Johannes
authors.initials: J
authors.lastname: Kapeller
authors.forename: Max
authors.initials: M
authors.lastname: Endele
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.forename: Susann
authors.initials: S
authors.lastname: Friedel
authors.forename: Mònica
authors.initials: M
authors.lastname: Gratacòs
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Manfred
authors.initials: M
authors.lastname: Fichter
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Aranda
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
authors.forename: Gudrun
authors.initials: G
authors.lastname: Rappold
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
mesh_terms: D000293:Adolescent; D001068:Feeding and Eating Disorders / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008954:Models, Biological; D010865:Pilot Projects; D011985:Receptors, Serotonin / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics* / Q000378:metabolism
chemical_list: D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3