Association between SCAP and SREBF1 gene polymorphisms and metabolic syndrome in schizophrenia patients treated with atypical antipsychotics

Abstract

Objectives: The use of atypical antipsychotics (AAPs) in the treatment of schizophrenia has been relevant because of the high prevalence of metabolic syndrome (MetS). The sterol-regulatory element-binding protein (SREBP) pathway may contribute to the underlying pathophysiology of AAP-induced metabolic adverse effects. We explored the association between the variants of the sterol-regulatory element-binding transcription factor-1 (SREBF1) gene and the SREBP cleavage-activation protein (SCAP) gene with AAP-induced MetS in a genetic case–control study. Methods: Eleven single nucleotide polymorphisms (SNPs) of SREBF1 and five of SCAP were genotyped in a Han Chinese population in Beijing, China: a sample of 722 schizophrenia patients on monotherapy with AAPs (clozapine, olanzapine or risperidone). Metabolic parameters were collected and evaluated for MetS criteria. Results: The rs11654081 T-allele of the SREBF1 gene was significantly associated with an increased risk for MetS after correction (P = 0.019, odds ratio, OR =2.56, 95% confidence interval, CI: 1.4 4–4.54). The rs11654081-TT genotype appeared more frequently in MetS than in non-MetS after correction (P = 0.026, OR =2.37, 95% CI: 1.3 6–4.12). SCAP polymorphisms with drug-induced MetS were negative in this study. Conclusions: The genetic polymorphisms of SREBF1 could play a role in the mechanism for interindividual variation of AAP-induced MetS.

Keywords:

• Metabolic syndrome
• antipsychotics
• schizophrenia
• SREBF
• SCAP

Acknowledgements

We are deeply grateful to all of the patients and healthy controls participating in this study as well as to the psychiatrists for their help in the recruitment and diagnosis of schizophrenic patients. This work was supported by the Natural Science Foundation of China (81171271), the Shanghai Municipal Natural Science Foundation (11ZR1431300), Shanghai Key Laboratory of Psychotic Disorders (13dz2260500) and the Research Project of Shanghai Health and Family Planning Commission (201440552).

Statement of interest

None to declare.