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Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia

Lin Yang1, Jianhua Chen2, Dengtang Liu2

  • 1Department of Psychiatry, Huashan Hospital, Fudan University, 200021 Shanghai, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|September 10, 2014
PubMed
Abstract

Insights

Genetic variations in the sterol regulatory element binding transcription factor 2 (SREBF2) gene are linked to metabolic syndrome (MetS) risk in schizophrenia patients treated with clozapine, indicating a potential genetic predisposition.

Area of Science:

  • Pharmacogenomics
  • Metabolic Disorders
  • Schizophrenia Treatment

Background:

  • Antipsychotic medications, particularly clozapine, are associated with metabolic side effects in schizophrenia patients.
  • Previous research suggests antipsychotics may activate the sterol regulatory element-binding protein (SREBP) pathway.
  • The sterol regulatory element binding transcription factor 2 (SREBF2) gene plays a key role in regulating cholesterol biosynthesis.

Purpose of the Study:

  • To investigate the association between SREBF2 gene polymorphisms and the risk of developing metabolic syndrome (MetS).
  • To examine the role of SREBF2 as a candidate gene for interindividual variations in drug-induced MetS.
  • To analyze SREBF2 gene polymorphisms in schizophrenia patients treated with clozapine.

Main Methods:

  • A genetic case-control study was conducted on 621 schizophrenia patients treated with clozapine.
  • Ten single nucleotide polymorphisms (SNPs) of the SREBF2 gene were genotyped in a Han Chinese population.
  • Patients were assessed for metabolic parameters and screened for MetS criteria.

Main Results:

  • The overall incidence of MetS was 41.8% (260/621) among the study participants.
  • Two SREBF2 markers (rs1052717 and rs2267443) showed a significant association with clozapine-induced MetS after FDR correction.
  • Carrying the A-allele of rs2267443 or rs1052717 increased the risk of MetS in patients treated with clozapine (OR=1.67-1.81).

Conclusions:

  • Genetic polymorphisms within the SREBF2 gene are potentially associated with the development of MetS in schizophrenia patients receiving clozapine.
  • These findings suggest SREBF2 may be a significant genetic factor influencing metabolic side effects of clozapine.
Keywords:
AntipsychoticsClozapineMetabolic syndromeSREBFSchizophrenia

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