Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia

• Genetic variants in SREBF2 gene may be associated with MetS induced by clozapine.
• Ten SNPs of SREBF2 were genotyped in schizophrenia patients treated with clozapine.
• rs1052717 and rs2267443 were associated with MetS induced by clozapine.

BackgroundPatients 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.MethodsTen 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.ResultsThe 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.ConclusionThe results suggest that the genetic polymorphisms of SREBF2 gene may be associated with MetS in patients treated with clozapine.