Association of ADRA2A and MTHFR gene polymorphisms with weight loss following antipsychotic switching to aripiprazole or ziprasidone

Hum Psychopharmacol. 2014 Jan;29(1):38-45. doi: 10.1002/hup.2366. Epub 2013 Nov 25.

Abstract

Objectives: 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).

Conclusion: 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.

Keywords: -1291C/G adrenergic receptor; 1298A/C methylenetetrahydrofolate reductase; antipsychotic-induced weight gain; aripiprazole; schizophrenia; ziprasidone.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Aripiprazole
  • Body Mass Index
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Polymorphism, Genetic
  • Quinolones / adverse effects
  • Quinolones / therapeutic use*
  • Receptors, Adrenergic, alpha-2 / genetics*
  • Schizophrenia / drug therapy
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use*
  • Weight Gain / drug effects
  • Weight Loss / genetics*

Substances

  • ADRA2A protein, human
  • Antipsychotic Agents
  • Piperazines
  • Quinolones
  • Receptors, Adrenergic, alpha-2
  • Thiazoles
  • ziprasidone
  • Aripiprazole
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)