title: Association of ADRA2A and MTHFR gene polymorphisms with weight loss following antipsychotic switching to aripiprazole or ziprasidone.
abstract: OBJECTIVE
  Various genetic polymorphisms have been reported to be associated with antipsychotic-induced weight gain. In this study, we aimed to determine whether risk polymorphisms in 12 candidate genes are associated with reduction in body mass index (BMI) of patients following switching of antipsychotics to aripiprazole or ziprasidone.
  
  
  METHODS
  We recruited 115 schizophrenia patients with metabolic abnormalities and who have been on at least 1 year treatment with other antipsychotics; they were then switched to either aripiprazole or ziprasidone. They were genotyped, and their BMI monitored for 6 months.
  
  
  RESULTS
  Significant associations with reduction in BMI at 6 months following switching were found in two of these genes: with rs1800544 of the ADRA2A gene (CC + CG [-0.32 ± 1.41 kg/m²] vs GG [-1.04 ± 1.63 kg/m²], p = 0.013) and with rs1801131 of the MTHFR gene (AA [-0.36 ± 1.53] vs AC + CC [-1.07 ± 1.53], p = 0.015).
  
  
  CONCLUSIONS
  The study data indicated that carriage of the ADRA2A rs1800544 GG genotype and the MTHFR rs1801131 C allele are associated with BMI reduction in this population following switching of antipsychotics to aripiprazole and ziprasidone.
authors.affiliation: Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Siti Norsyuhada
authors.initials: SN
authors.lastname: Roffeei
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Reynolds
authors.forename: Nor Zuraida
authors.initials: NZ
authors.lastname: Zainal
authors.forename: Mas Ayu
authors.initials: MA
authors.lastname: Said
authors.forename: Ahmad
authors.initials: A
authors.lastname: Hatim
authors.forename: Syarinaz Ahmad
authors.initials: SA
authors.lastname: Aida
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000068180:Aripiprazole; D015992:Body Mass Index; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects; D015431:Weight Loss / Q000235:genetics*
chemical_list: C547768:ADRA2A protein, human; D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D018341:Receptors, Adrenergic, alpha-2; D013844:Thiazoles; C092292:ziprasidone; D000068180:Aripiprazole; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: -1291C/G adrenergic receptor; 1298A/C methylenetetrahydrofolate reductase; antipsychotic-induced weight gain; aripiprazole; schizophrenia; ziprasidone