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. CONCLUSION: The results suggest that the genetic polymorphisms of SREBF2 gene may be associated with MetS in patients treated with clozapine.