title: Effect of FTO, SH2B1, LEP, and LEPR polymorphisms on weight gain associated with antipsychotic treatment.
abstract: Weight gain is one of the major adverse effects of antipsychotics. Although mechanisms remain unclear, genetic susceptibility has become increasingly attractive as a potential mechanism that could explain a significant part of interindividual variability. Most investigations have explored genes related with the mechanism of action of antipsychotic drugs. An alternative approach to investigate the role that genetic factors play in weight gain secondary to antipsychotic treatment is to study those genetic variants that have been found associated with obesity. The aim of this study was to determine whether the fat mass and obesity-associated gene (FTO) rs9939609 variant, the single nucleotide polymorphism that has shown the strongest association with common obesity in different populations, influences weight gain during the first year of antipsychotic treatment. We investigated also the genetic variants in other 3 strong candidates genes involved in the leptin-signaling pathway including leptin, leptin receptor, and Src homology 2. We carried out a prospective study on 239 patients with first-episode psychosis. Two hundred five patients completed the follow-up at 1 year (85.8%). Before antipsychotic treatment, the homozygous subjects for the risk allele A of the FTOrs9939609 variant had a higher body mass index at baseline (24.2 T 3.8 kg/m²) than the AT/TT group (22.82 T 3.3 kg/m2; F = 5.744; P = 0.018). After 1 year, the magnitude of weight increase was similar in the 3 genotypes defined by the rs9939609 variant. These results suggest that the pharmacological intervention accompanied by changes in energy intake and expenditure could suppress the genetic susceptibility conferred by the FTO genotype. None of the other single nucleotide polymorphisms evaluated were associated with weight gain during the first 12 months of antipsychotic therapy.
authors.affiliation: Department of Psychiatry, Marqués de Valdecilla University Hospital, Planta 2(a), Edificio 2 de Noviembre, Avda. Valdecilla s/n, 39008 Santander, Spain. rperez@humv.es
authors.forename: Rocio
authors.initials: R
authors.lastname: Perez-Iglesias
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mata
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Amado
authors.forename: Ana
authors.initials: A
authors.lastname: Berja
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Garcia-Unzueta
authors.forename: Obdulia
authors.initials: O
authors.lastname: Martínez García
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Arranz
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Vazquez-Barquero
authors.forename: Benedicto
authors.initials: B
authors.lastname: Crespo-Facorro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D011618:Psychotic Disorders / Q000188:drug therapy; D054411:Receptors, Leptin / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014150:Antipsychotic Agents; D020738:Leptin; D011506:Proteins; D054411:Receptors, Leptin; C518910:SH2B1 protein, human; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human