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Association study of MDR1 and 5-HT2C genetic polymorphisms and antipsychotic-induced metabolic disturbances in female

M R Kuzman1, V Medved, N Bozina

  • 1Department of Psychiatry, University Hospital Centre Zagreb and Zagreb School of Medicine, Zagreb, Croatia. mrojnic@gmail.com

The Pharmacogenomics Journal
|March 3, 2010
PubMed

Insights

Specific gene variants in serotonin 2C receptor (5-HT2C) and multidrug resistant protein (MDR1) are linked to metabolic changes in women with schizophrenia treated with antipsychotics.

Area of Science:

  • Pharmacogenetics
  • Psychiatry
  • Metabolic Disorders

Background:

  • Antipsychotic medications, such as olanzapine and risperidone, are associated with metabolic abnormalities.
  • Genetic variations in serotonin 2C receptor (5-HT2C) and multidrug resistant protein 1 (MDR1) may influence treatment response and side effects.
  • Previous research indicated associations between these genetic polymorphisms and weight gain in schizophrenia patients.

Purpose of the Study:

  • To investigate the association between 5-HT2C and MDR1 gene polymorphisms and antipsychotic-induced metabolic abnormalities.
  • To analyze the impact of specific genetic variants (-759CT 5-HT2C, G2677T, C3435T MDR1) on metabolic parameters in female schizophrenia patients.
  • To assess changes in glucose, lipid profiles, blood pressure, and waist circumference over a 3-month treatment period.

Main Methods:

  • A cohort of 101 previously non-medicated female patients with schizophrenia spectrum disorders were enrolled.
  • Patients were treated with olanzapine or risperidone for 3 months.
  • Fasting glucose, lipid profiles, blood pressure, and waist circumference were measured and analyzed in relation to 5-HT2C and MDR1 genotypes.

Main Results:

  • The -759T 5-HT2C variant was significantly associated with increased waist circumference, fasting glucose, and triglyceride levels.
  • MDR1 variants (2677T and 3435T) showed a significant association with increased fasting glucose levels during olanzapine treatment.
  • These genetic polymorphisms may influence the development of metabolic abnormalities in patients treated with olanzapine/risperidone.

Conclusions:

  • Genetic variations in 5-HT2C and MDR1 play a potential role in antipsychotic-induced metabolic disturbances.
  • Pharmacogenetic profiling could aid in predicting and managing metabolic side effects in schizophrenia treatment.
  • Further research is warranted to elucidate the precise mechanisms underlying these genetic associations.

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