Association of FTO, LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics

Pharmacogenomics. 2014 Mar;15(4):477-85. doi: 10.2217/pgs.13.220.


Aim: The occurrence of metabolic syndrome (MS) in schizophrenia patients receiving long-term antipsychotics (APs) contributes to their high mortality rate. We aimed to determine whether genetic polymorphisms of identified candidate genes are associated with MS in our study population.

Materials & methods: We recruited 206 schizophrenia patients receiving AP treatment for at least a year. Cross-sectional measurements of weight, height, blood pressure, waist and hip circumference, and other lipid profiles were recorded. Patient DNA was genotyped for 16 candidate gene polymorphisms.

Results: Of these patients, 59.7% were found to have MS while 40.3% did not. All metabolic parameters were significantly different between the two groups. Only three of the 16 polymorphisms studied showed significant association with MS; rs9939609 of the FTO gene confers risk for MS (odds ratio [OR]: 1.73, 95% CI: 1.07-2.78, p = 0.026), while rs1137101 of the LEPR gene (OR: 0.47, 95% CI: 0.28-0.80, p = 0.005) and rs1801133 of the MTHFR gene (OR: 0.59, 95% CI: 0.35-0.99, p = 0.049) are protective against MS.

Conclusion: Polymorphisms of the FTO, LEPR and MTHFR genes may play a role in MS in Malaysian schizophrenia patients receiving long-term treatment with APs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Humans
  • Male
  • Metabolic Syndrome / chemically induced
  • Metabolic Syndrome / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Proteins / genetics*
  • Receptors, Leptin / genetics*
  • Risk
  • Schizophrenia / drug therapy*
  • Schizophrenia / genetics


  • Antipsychotic Agents
  • LEPR protein, human
  • Proteins
  • Receptors, Leptin
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)