MODULAÇÃO DA EXPRESSÃO DO GENE DA METILENOTETRAHIDROFOLATO REDUTASE (MTHFR) EM REPOSTA AO TRATAMENTO CLÍNICO EM CRIANÇAS COM TEA

Abstract

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by deficits in communication, social interaction, and repetitive behaviors, with an increasing prevalence over recent decades. Genetic, epigenetic, and inflammatory factors, such as dysregulation of folate metabolism and elevated pro-inflammatory cytokines, are implicated in its pathophysiology. Objective: This study evaluated the expression of the MTHFR gene and the inflammatory marker TNF-α in children with ASD undergoing experimental pharmacological treatment. Methodology: Two randomized double-blind clinical trials were conducted with blood collection from children with Autism Spectrum Disorder (GTEA1 and GTEA2), along with a cross-sectional study using buccal epithelial cells from typically developing children (GTYPICAL). Patients were distributed into three groups: GTEA1 (n = 20), GTEA2 (n = 30), and GTYPICAL (n = 4). GTEA1 and GTEA2 comprised patients receiving pharmacological treatment. RNA was extracted using the Trizol method, followed by cDNA synthesis and real-time PCR. Results and Discussion: In GTEA1, a significant reduction in TNF-α levels was observed in treated individuals (t-test, p = 0.0395). In GTEA2, regarding the relative expression of the MTHFR gene, there was a significant increase when comparing treated versus untreated versus placebo (ANOVA, p = 0.009), treated versus untreated (t-test, p = 0.0289), and placebo versus treated (t-test, p = 0.065). No significant difference was found between placebo versus untreated (t-test, p = 0.7422). Concerning TNF-α, the reduction in relative expression was only observed between treated versus placebo (t-test, p = 0.0241), suggesting a positive impact of treatment on metabolic and inflammatory processes. Amplification curve analysis demonstrated 100% efficiency and high linearity for the MTHFR gene, the target of this research. The findings support the feasibility of using buccal cells in GTYPICAL as a non-invasive sample for molecular analysis and suggest that modulation of folate metabolism may be associated with clinical improvement in patients with ASD. Conclusion: The results provide relevant insights into the molecular basis of ASD and contribute to the development of personalized therapeutic strategies. Descriptors: Autism Spectrum Disorder; Folate; MTHFR; TNF-α.