Drug-naive patients with schizophrenia have metabolic disorders that are not associated with polymorphisms in the LEP (-2548G/A) and 5-HTR2C (-759C/T) genes.

Schizophrenia is a mental disorder that is primarily caused by polygenic mutations. Schizophrenic patients are more likely to suffer from metabolic syndrome (MS), which is usually accompanied by polymorphisms in the leptin (LEP) gene at the -2548 (G/A) locus and the 5-hydroxytryptamine receptor 2C (5-HTR2C) gene at the -759 (C/T) locus. Hence, we hypothesized an association between these polymorphisms and schizophrenia incidence. A total of 148 drug-naive schizophrenic patients and 165 normal controls were enrolled in the study. Blood glucose levels, lipid levels, and other metabolic markers were measured. MALDI-TOFMS was performed to analyse genotypes of LEP and 5-HTR2C at -2548 (G/A) and -759 (C/T) loci, respectively. Patients with first-episode schizophrenia showed higher levels of fasting blood glucose and the 2-h postprandial glucose (2 hPG), as well as higher insulin resistance indices, but showed lower high-density lipoprotein cholesterol (HDL-C) levels compared to those of the controls. The above results were partly observed when the analysis was performed separately in males and females. Schizophrenic and healthy participants showed no significant differences in the genotypes and allele frequencies in the leptin and 5-HTR2C genes. Patients with varying genotypes of -2548 (G/A) in the leptin gene and -759 (C/T) in the 5-HTR2C gene showed no differences in the indices related to the glucose and lipid metabolism. Taken together, drug-naive schizophrenia patients showed some incidence of metabolic disorders, but polymorphisms in the LEP (-2548G/A) and 5-HTR2C (-759C/T) genes were not associated with schizophrenia or metabolic disorders.