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

Pharmacogenomics J. 2011 Feb;11(1):35-44. doi: 10.1038/tpj.2010.7. Epub 2010 Mar 2.

Abstract

The objective of this study was to determine the association of 5-HT2C (serotonin 2C receptor) and MDR1 (multidrug resistant protein) genetic polymorphisms and antipsychotic-induced metabolic abnormalities among female patients with DSM IV schizophrenia spectrum disorders. We have previously reported the associations of -759CT 5-HT2C and G2677T and C3435T MDR1 genetic polymorphisms and olanzapine/risperidone-induced weight gain in a similar sample of patients. Here, we included a total of 101 previously non-medicated female patients treated with olanzapine/risperidone over a 3-month period. The variables analyzed included fasting glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglyceride levels in blood, blood pressure and waist circumferences. We observed significant association of -759T 5-HT2C genetic variant and greater increase in waist circumference (P=0.03), fasting glucose level (P=0.046) and triglyceride level (P=0.045) in blood after a 3-month period. The 2677T and 3435T MDR1 genetic variants were significantly associated with the greater increase in fasting glucose level in blood when patients were using olanzapine (P<0.001 and P=0.028, respectively). Our data indicate a possible influence of -759CT 5-HT2C and MDR1 G2677T and C3435T MDR1 genetic polymorphisms on the development of metabolic abnormalities among female patients treated with olanzapine/risperidone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Blood Glucose / metabolism
  • Cohort Studies
  • Female
  • Humans
  • Middle Aged
  • Olanzapine
  • Polymorphism, Genetic
  • Receptor, Serotonin, 5-HT2C / genetics*
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Risperidone / adverse effects
  • Risperidone / therapeutic use
  • Schizophrenia / drug therapy*
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Waist Circumference
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antipsychotic Agents
  • Blood Glucose
  • Receptor, Serotonin, 5-HT2C
  • Benzodiazepines
  • Risperidone
  • Olanzapine