title: Pharmacogenomics of sterol synthesis and statin use in schizophrenia subjects treated with antipsychotics.
abstract: OBJECTIVE
  Patients with schizophrenia treated with antipsychotics often develop metabolic side effects including dyslipidemia. Antipsychotics potentially upregulate gene expression of a lipid metabolism pathway protein called SREBP via SREB transcription factors (SREBFs). Genetic variation within SREBF may contribute to dyslipidemias and lipid medication efficacy within schizophrenia.
  
  
  RESULTS
  A cross-sectional study of 157 patients were genotyped for SREBF1 (rs11868035) and SREBF2 (rs1057217) variants, and assessed for fasting lipids. The cohort's mean age was 46.6 years, was 64% male and 86% were using atypical antipsychotics. When stratified by statin use, those receiving a statin and carrying the SREBF1 T allele exhibited higher total cholesterol levels (p = 0.01), triglyceride levels (p = 0.04) and low-density lipoprotein levels (p = 0.03). A regression analysis controlling for gender differences in lipids showed that the SREBF1 T allele and statin interaction remained only for total cholesterol levels (F[4,149] = 5.8; p < 0.0001).
  
  
  CONCLUSIONS
  For schizophrenia individuals with the SREBF1 rs11868035 T allele, incomplete response to statin medications may be seen. Future investigations may allow for personalizing dyslipidemia treatment based on pharmacogenetics within schizophrenia.
authors: Clinical & Translational Pharmacy, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
authors: Thomas J
authors: TJ
authors: Vassas
authors: Kyle J
authors: KJ
authors: Burghardt
authors: Vicki L
authors: VL
authors: Ellingrod
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002784:Cholesterol / Q000378:metabolism; D050171:Dyslipidemias / Q000139:chemically induced / Q000235:genetics; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051779:Sterol Regulatory Element Binding Proteins; D013261:Sterols; D002784:Cholesterol