Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders.

Autor:	Mayén-Lobo YG; Master's Program in Pharmaceutical Sciences, Universidad Autónoma Metropolitana, Campus Xochimilco, Mexico City, Mexico., Alcaraz-Zubeldia M; Department of Neurochemistry, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez (INNN), Mexico City, Mexico., Dávila-Ortiz de Montellano DJ; Department of Genetics, INNN, Mexico City, Mexico., Motilla-Frías BA; Department of Genetics, INNN, Mexico City, Mexico., García-Manteca MY; Department of Genetics, INNN, Mexico City, Mexico., Ortega-Vázquez A; Department of Biological Systems, Universidad Autónoma Metropolitana, Campus Xochimilco, Mexico City, Mexico., Aviña-Cervantes CL; Department of Psychiatry, INNN, Manuel Velasco Suárez, Mexico City, Mexico., Crail-Meléndez ED; Department of Psychiatry, INNN, Manuel Velasco Suárez, Mexico City, Mexico., Ríos C; Department of Neurochemistry, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez (INNN), Mexico City, Mexico. Department of Biological Systems, Universidad Autónoma Metropolitana, Campus Xochimilco, Mexico City, Mexico., López-López M; Department of Biological Systems, Universidad Autónoma Metropolitana, Campus Xochimilco, Mexico City, Mexico., Monroy-Jaramillo N; Department of Genetics, INNN, Mexico City, Mexico.
Jazyk:	angličtina
Zdroj:	Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) [Braz J Psychiatry] 2023 May 11; Vol. 45 (2), pp. 117-126. Date of Electronic Publication: 2023 May 11.
DOI:	10.47626/1516-4446-2022-2783
Abstrakt:	Objective: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. Methods: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. Results: GSH levels were significantly reduced and, conversely, GPx activity was higher in PD patients compared to controls. GCLC_GAG-7/9 genotype (OR=4.3, CI95=1.40-14.31, p=0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR=6.09, CI95=1.93-22.59, p=0.003) were found as risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or to metabolic ratio. Conclusions: GCLC variants were associated with the oxidative stress profile of PD patients raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal. Competing Interests: The authors report no conflicts of interest.
Databáze:	MEDLINE
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