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). CONCLUSION: 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.
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). CONCLUSION: For schizophrenia individuals with the SREBF1rs11868035 T allele, incomplete response to statin medications may be seen. Future investigations may allow for personalizing dyslipidemia treatment based on pharmacogenetics within schizophrenia.
Authors: M Fiegenbaum; F R Silveira; C R Van der Sand; L C Van der Sand; M E W Ferreira; R C Pires; M H Hutz Journal: Pharmacogenomics J Date: 2005 Impact factor: 3.550
Authors: Joseph P McEvoy; Jonathan M Meyer; Donald C Goff; Henry A Nasrallah; Sonia M Davis; Lisa Sullivan; Herbert Y Meltzer; John Hsiao; T Scott Stroup; Jeffrey A Lieberman Journal: Schizophr Res Date: 2005-08-30 Impact factor: 4.939
Authors: J Fernø; M B Raeder; A O Vik-Mo; S Skrede; M Glambek; K-J Tronstad; H Breilid; R Løvlie; R K Berge; C Stansberg; V M Steen Journal: Pharmacogenomics J Date: 2005 Impact factor: 3.550
Authors: Brenda Vincenzi; Christina Pc Borba; Deborah A Gray; Paul M Copeland; Xingyue Wang; Xiaoduo Fan; Gowri G Aragam; David C Henderson Journal: Ann Clin Psychiatry Date: 2013-05 Impact factor: 1.567