Tobacco use modify exon IV BDNF gene methylation levels in depression.

This study aimed to investigate BDNF gene methylation in individuals with depression based on tobacco use. Therefore, 384 adults from southeastern Brazil were recruited to assess depression, socioeconomic status, lifestyle, and methylation by pyrosequencing exon IV promoter region of the BDNF gene. The Generalized Linear Model (GzLM) was used to check the effect of depression, tobacco, and the interaction between depression and tobacco use in methylation levels. In addition, the Kruskal-Wallis test, followed by Dunn's post hoc test, was used to compare methylation levels. Interaction between depression and tobacco use was significant at levels of BDNF methylation in the CpG 5 (p = 0.045), 8 (p = 0.016), 9 (p = 0.042), 10 (p = 0.026) and mean 5-11 (p < 0.001). Dunn's post hoc test showed that individuals with depression and tobacco use compared to those with or without depression who did not use tobacco had lower levels of BDNF methylation in CpG 5, 6, 7, 8, 9, 11, and mean 5-11. Therefore, we suggest that tobacco use appears to interfere with BDNF gene methylation in depressed individuals.

Methylation of the NR3C1 gene in individual with chronic pain: patient profile in a cross-sectional study with users of the public health system / Metilação do gene NR3C1 em indivíduos com dor crônica: perfil de pacientes em estudo transversal com usuários do sistema público de saúde

ABSTRACT BACKGROUND AND OBJECTIVES: Studies suggest that shared molecular factors can simultaneously affect different chronic pain syndromes. Understanding the epigenetic mechanisms of various diseases that are associated with chronic pain is essential to comprehend its appearance and progression. The objective of this study is to evaluate the association between DNA methylation of the NR3C1 gene with the presence and intensity of chronic pain, as well as predictive factors also considering socioeconomic, health and lifestyle factors correlated with this association, in adult individuals using the Brazilian Unified Health System (Sistema Único de Saúde - SUS) in a municipality in Southeast Brazil. METHODS: This is a cross-sectional study, whose data collection was carried out through interviews to investigate socioeconomic status, lifestyle and health conditions, in addition to anthropometric assessments and blood samples. Data were analyzed by quantitative DNA methylation assays and statistical analysis. CONCLUSION: The findings suggest epigenetic involvement in NR3C1 gene methylation in association with chronic pain and suggest the need to seek new evidence in relation to the mechanisms that explain chronic pain, especially from an epigenetic point of view, as they may provide subsidies for the prevention and control of chronic pain targeting individuals with the profile found in this study.

RESUMO JUSTIFICATIVA E OBJETIVOS: Estudos sugerem que fatores moleculares compartilhados podem afetar simultaneamente diferentes síndromes de dor crônica. Compreender os mecanismos epigenéticos de várias doenças que estão associadas à dor crônica é essencial para entender sua aparência e progressão. O objetivo deste estudo foi avaliar a associação entre metilação do DNA do gene NR3C1, receptor de glicocorticoides, com a presença e intensidade de dor crônica, bem como os fatores preditivos considerando também fatores socioeconômicos, de saúde e de estilo de vida correlacionados com tal associação em pacientes adultos usuários do Sistema Único de Saúde (SUS) em um município do sudeste brasileiro. MÉTODOS: Trata-se de um estudo observacional transversal, cuja coleta de dados foi realizada através de entrevistas para investigação do status socioeconômico, condições de estilo de vida e de saúde, além de avaliações antropométricas e coletas de sangue. Os dados foram analisados por meio de ensaios quantitativos de metilação do DNA e análise estatística. RESULTADOS: Foi observado que 123 participantes (44,1%) apresentaram metilação da região estudada do gene NR3C1. Análises estatísticas univariadas e multivariada mostraram que as variáveis idade e nível de cortisol estão significativamente associadas com a metilação do gene e a presença de dor crônica. CONCLUSÃO: Os achados sugerem envolvimento epigenético na metilação do gene NR3C1 em associação com dor crônica e sugerem a necessidade de se buscar novas evidências em relação aos mecanismos que explicam a dor crônica, sobretudo do ponto de vista epigenético, pois as mesmas poderão trazer subsídios para prevenção e controle da dor crônica visando pacientes com o perfil encontrado nesse estudo.

Lifestyle and NR3C1 exon 1F gene methylation is associated with changes in glucose levels and insulin resistance.

AIMS: the present study aimed to investigate how glucose and insulin levels may be associated with changes in NR3C1 gene methylation levels in adults. MAIN METHODS: 375 volunteers users of the Brazilian Public Unified Health System (SUS) were recruited to assess socioeconomic status, lifestyle, anthropometric data, blood glucose and serum cortisol levels, insulin resistance, and NR3C1 gene methylation assessment. Factors associated with glucose levels and insulin resistance were investigated using multivariate analysis GLzM at 5% significance (p<0.05). KEY FINDINGS: our results verified that glucose levels and insulin resistance were directly related to NR3C1 gene methylation and age, while not being overweight and obese and no tobacco consumption were indirectly related to glucose levels and insulin resistance. SIGNIFICANCE: habits and lifestyle may influence NR3C1 gene regulation, revealing the complexity of environmental impacts on NR3C1 methylation. Furthermore, associated risk factors must be taken into account in epigenetic studies as they directly interfere with blood glucose levels and insulin resistance.

Food and nutritional insecurity is associated with depressive symptoms mediated by NR3C1 gene promoter 1F methylation.

The aim of this study was to investigate socioeconomic stressors predictive of depressive symptoms and possible epigenetic changes in the glucocorticoid receptor - NR3C1-1F - an encoding gene involved in depressive symptoms. A total of 321 adult volunteers from southeastern Brazil were recruited to evaluate depressive symptoms, socio-demographic and economic factors, including food and nutritional security (FNS) or insecurity (FNiS) status, and NR3C1-1F region methylation by pyrosequencing. Depressive symptom determinants were investigated using a Poisson regression model with robust variance. Mann-Whitney tests and structural mediation equation models were used to evaluate the relationship between NR3C1 DNA methylation, FNiS, and depressive symptoms. Multivariate Poisson regression with robust variance adjusted for sex and FNiS and NR3C1-1F region methylation predicted risk factors for depressive symptoms. Mediation analysis revealed that NR3C1-1F region methylation mediated the relationship between FNiS exposure and depressive symptoms as an outcome, and depressive volunteers and FNiS individuals exhibited a significant increase in NR3C1 methylation when compared to healthy individuals and FNS volunteers, respectively. Therefore, we suggest that stress caused by FNiS may lead to depressive symptoms and that NR3C1-1F DNA methylation can act as a mediator of both FNiS and depressive symptoms.

Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association.

OBJECTIVE: The aim of this study was to verify determinant factors for depression and analyze the relationship between possible changes in HPA axis and depression, in this case NR3C1 DNA methylation and serum cortisol levels. METHODS: 349 adult volunteers were recruited to evaluate depression, socio-demographic, economic and lifestyle factors, serum cortisol levels and NR3C1 DNA methylation by pyrosequencing. Depression determinant factors were investigated using a Poisson regression model with robust variance (p < 0.05). RESULTS: Poisson regression with robust variance adjusted by gender, tobacco use, self-perceived stress, leisure activity, suicidal ideation, low cortisol levels and NR3C1 DNA methylation was performed and predicted risk factors for depression. Furthermore, depressive volunteers showed a significant increase in NR3C1 DNA methylation when compared to healthy volunteers. CONCLUSIONS: This findings provide a basis for understanding the role of HPA axis in depression, especially its regulation by NR3C1 DNA methylation. Furthermore, it emphasizes the stressful lifestyle risk factors (female, tobacco uso, self perceived stress, leisure activities absence and suicidal ideation) that can contribute to future research and the search for public health policies to improve quality of live, mental and general health.