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Purpose: Oxidative stress contributes to the development of schizophrenia and metabolic abnormalities among schizophrenia patients. This study investigated whether the oxidative stress-related genes polymorphisms affected the risk for metabolic abnormalities among schizophrenia patients or not. Methods: A cross-sectional analysis was conducted among 256 schizophrenia patients and 194 ageand gender-matched controls. The effects of the polymorphisms of methylenetetrahydrofolate reductase (MTHFR ) (rs1801133, C677T; rs1801131, A1298C) and glutathione S-transferase (GST)T1 null, GSTM1 null, GSTK1 (rs1917760, G-1308T) on the risk for metabolic abnormalities were investigated by structural equation modeling. Results: Among the female schizophrenia patients, the MTHFR rs1801133 T/T genotype increased the risk of overweight, and this genotype effect was associated with a risk of metabolic abnormalities. Among the schizophrenia patients with current-smoking status, the MTHFR rs1801133 T/T genotype also increased the risk of overweight, thus affecting the risk of metabolic abnormalities. The effects of GSTK1 T allele carriers and GSTM1 null genotypes on the increased risk of overweight were confirmed in the male schizophrenia patients and/or the patients with current-smoking status. In contrast, no association between the polymorphisms and risk of metabolic abnormalities was observed in control subjects. Discussion: These findings suggest that the polymorphisms of oxidative stress-related genes, including MTHFR , may be a significant risk factor for overweight-related metabolic abnormalities among schizophrenia patients in relation to gender differences and/or smoking status. This information regarding the effect of high-risk genotypes may be used to prevent overweight and metabolic abnormalities.

Association between oxidative stress-related genes polymorphisms and metabolic abnormalities among schizophrenia patients