RESUMEN
Background: In this study, we aimed to investigate the effects of polymorphisms in genes encoding 1-carbon metabolism enzymes on differential development of metabolic parameters during 12 weeks of treatment with second-generation antipsychotics in first-episode schizophrenia patients. Methods: The following polymorphisms in 1-carbon metabolism genes were genotyped: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G), and BHMT (G742A). A broad panel of metabolic parameters including body mass index, waist circumference, total cholesterol low and high density lipoproteins, triglycerides, homocysteine, folate, and vitamin B12 was determined. Results: There was a significant effect of the interaction between the MTHFR C677T polymorphism and time on body mass index and waist circumference in the allelic and genotype analyses. Indeed, patients with the MTHFR 677CC genotype had higher increase in body mass index and waist circumference compared with other corresponding genotypes or the MTHFR 677T allele carriers (CT and TT genotypes). In addition, patients with the MTHFR 677TT genotype had higher waist circumference in all time points. Similarly, patients with the MTHFR 677TT genotype had higher body mass index in all time points, but this effect was not significant after correction for multiple testing. Conclusions: Our results indicate that the MTHFR C677T polymorphism may predict antipsychotic-induced weight gain. Effects of the MTHFR C677T polymorphism might be different in initial exposure to antipsychotics compared with long-term perspective.
Asunto(s)
Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético/genética , Esquizofrenia/genética , Adulto , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Betaína-Homocisteína S-Metiltransferasa/genética , Índice de Masa Corporal , Femenino , Ferredoxina-NADP Reductasa/genética , Genotipo , Humanos , Masculino , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Antígenos de Histocompatibilidad Menor/genética , Esquizofrenia/tratamiento farmacológico , Circunferencia de la Cintura/efectos de los fármacos , Circunferencia de la Cintura/genética , Adulto JovenRESUMEN
The aim of this study was to investigate the prevalence of metabolic disturbances in patients with first-episode schizophrenia (FES) and test the hypothesis that genetic variation in one-carbon metabolism may account for metabolic dysregulation in early psychosis. We measured fasting glucose, lipid profile parameters, homocysteine, folate and vitamin B12 in 135 patients with FES and 146 healthy controls (HCs). Polymorphisms in the following genes were determined: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G) and BHMT (G742A). Serum levels of folate and high-density lipoproteins (HDL) were significantly lower in patients with FES compared to HCs. In turn, serum levels of homocysteine and triglycerides were significantly higher in patients with FES than in HCs. Prevalence of hyperhomocysteinemia, low folate and HDL levels together with dyslipidemia was significantly higher in patients with FES compared to HCs. Higher homocysteine levels, lower vitamin B12 levels and the presence of metabolic syndrome were associated with higher severity of negative symptoms. None of studied polymorphisms was associated with schizophrenia risk. Several associations between studied polymorphisms and cardio-metabolic parameters were found. None of them remained significant after Bonferroni correction. Our results indicate that metabolic dysregulation in patients with FES is not associated with genetic variation in one-carbon metabolism.