title: Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia.
abstract: BACKGROUND
  Patients with schizophrenia using antipsychotics often develop metabolic side effects, especially with clozapine. Previous studies indicated that antipsychotics could activate the pathway of the sterol regulatory element-binding protein (SREBP). The sterol regulatory element binding transcription factor 2 (SREBF2) gene mainly regulates the cholesterol biosynthetic gene. Therefore, we hypothesized that the SREBF2 gene would be a candidate gene for interindividual variation in drug-induced metabolic syndrome (MetS). In this genetic case-control study, we examined the SREBF2 gene polymorphisms in the risk of MetS patients treated with clozapine.
  
  
  METHODS
  Ten single nucleotide polymorphisms (SNPs) of SREBF2 were genotyped in a CHB (Han Chinese in Beijing, China) population, a sample of 621 schizophrenia patients treated with clozapine. Patients were evaluated for metabolic parameters and screened for the MetS criteria.
  
  
  RESULTS
  The incidence of MetS among all subjects was 41.8% (260/621). Two markers of SREBF2 were associated with MetS induced by clozapine after False Discovery Rate (FDR) correction (rs1052717, corrected Pallele=0.010, corrected Pgenotype=0.022; and rs2267443, corrected Pgenotype=0.015). Patients who received clozapine and carried the A-allele of rs2267443 or rs1052717 had an increased risk of MetS (rs2267443, odds ratio (OR)=1.67, 95% confidence interval (CI): 1.20-2.34; and rs1052717, OR=1.81, 95% CI: 1.15-1.98), adjusted by logistic regression for clinical characteristics.
  
  
  CONCLUSIONS
  The results suggest that the genetic polymorphisms of SREBF2 gene may be associated with MetS in patients treated with clozapine.
authors.affiliation: Department 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Dengtang
authors.initials: D
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Shunying
authors.initials: S
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Enzhao
authors.initials: E
authors.lastname: Cong
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Haisu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Shanghai Luwan Mental Health Center, 1162 Quxi Road, 200023 Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Zuo
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200030 Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Huashan Hospital, Fudan University, 200021 Shanghai, China.
authors.forename: Shiqiao
authors.initials: S
authors.lastname: Liang
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes (Ministry of Education), Shanghai Jiao Tong University, 200030 Shanghai, China).
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department 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.
authors.forename: Shenxun
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department 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. Electronic address: hyyyyb@gmail.com.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D003024:Clozapine / Q000009:adverse effects*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D003024:Clozapine
keywords: Antipsychotics; Clozapine; Metabolic syndrome; SREBF; Schizophrenia