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Estado de metilación de regiones promotoras de tres genes de respuesta inflamatoria en una muestra de colombianos con problemas de consumo de alcohol: un estudio exploratorio
Methylation status of promoter regions of three inflammatory response genes in a sample of Colombians with alcohol consumption problems - an exploratory study
Estado de metilação de regiões promotoras de três genes de resposta inflamatória em uma amostra de colombianos com problemas de consumo de álcool – um estudo exploratório
DOI:
https://doi.org/10.15446/rcciquifa.v53n1.110956Palabras clave:
Metilación, modificación con bisulfito, respuesta inflamatoria, ALCOHOL, SNCA, MIF, IFNGR1 (es)Methylation, bisulfite modification, inflammatory response, alcohol, SNCA, MIF, IFNGR1 (en)
Metilação, modificação de bissulfito, resposta inflamatória, álcool, SNCA, MIF, IFNGR1 (pt)
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Introducción: La dependencia del alcohol exhibe un patrón de herencia multifactorial. Las vías de respuesta inflamatoria han despertado un interés particular, específicamente el aspecto epigenético está muy influenciado étnicamente y por la evolución personal de la enfermedad. Objetivo: Comparar el estado de metilación de una región promotora con islas CpG de algunos genes candidatos a dianas farmacéuticas en la vía de respuesta inflamatoria, entre controles e individuos con consumo problemático de alcohol de una muestra de una población universitaria colombiana. Métodos: Previamente, se realizaron estudios sobre 29 variantes genéticas que afectan a 10 genes implicados en la respuesta inflamatoria. Luego se realizó análisis de la expresión de ARNm y proteínas de algunos de estos genes, perfilando a tres genes para estudios de metilación, a saber, SNCA, MIF e IFNGR1. Se analizó el estado de metilación del ADN modificado con bisulfito mediante PCR con marcaje fluorescente, electroforesis capilar y validación con secuenciación de Sanger. Resultados: Existen cambios en el estado de metilación del promotor de los genes MIF y SNCA en los casos. Se observó concordancia entre la expresión génica y el estado de metilación en MIF en la muestra general, y también con la síntesis de ARNm-SNCA, sin cambios apreciables en la proteína, aunque con diferencias según el sexo. Conclusión: Nuestro estudio proporcionó información sobre el estado de metilación de los promotores SNCA y MIF y su relación con la expresión génica en fenotipos de consumo problemático de alcohol. Estas dos proteínas se proponen como candidatas para estudios de modelado.
Introduction: Alcohol dependence exhibits a multifactorial inheritance pattern. The inflammatory response pathways have aroused particular interest, specifically the epigenetic aspect is highly influenced by ethnicity and by the personal evolution of the disease. Objective: To compare the methylation status of a promoter region with CpG islands of some candidate genes for pharmaceutical targets in the inflammatory response pathway, between controls and individuals with problematic alcohol consumption from a sample of a Colombian university population. Methods: Previously, studies were carried out on 29 genetic variants that affect 10 genes involved in the inflammatory response. Analysis of the mRNA and protein expression of some of these genes was then performed, profiling three genes for methylation studies, namely SNCA, MIF, and IFNGR1. The methylation status of bisulfite-modified DNA was analyzed by PCR with fluorescent labeling, capillary electrophoresis, and validation with Sanger sequencing. Results: There are changes in the methylation state of the promoter of the MIF and SNCA genes in the cases. Concordance was observed between gene expression and methylation status in MIF in the general sample, and also in the synthesis of mRNA-SNCA, without appreciable changes in the protein, although with differences according to sex. Conclusion: Our study provided information on the methylation status of the SNCA and MIF promoters and its relationship with expression in problem drinking phenotypes. These two proteins are proposed as candidates for modeling studies.
Introdução: A dependência do álcool apresenta um padrão de herança multifatorial. As vias de resposta inflamatória têm despertado particular interesse, especificamente o aspecto epigenético é altamente influenciado etnicamente e pela evolução pessoal da doença. Objetivo: Comparar o estado de metilação de uma região promotora com ilhas CpG de alguns genes candidatos a alvos farmacêuticos na via de resposta inflamatória, entre controles e indivíduos com consumo problemático de álcool de uma amostra de uma população universitária colombiana. Métodos: Anteriormente, foram realizados estudos com 29 variantes genéticas que afetam 10 genes envolvidos na resposta inflamatória. A análise do mRNA e da expressão proteica de alguns desses genes foi então realizada, traçando o perfil de três genes para estudos de metilação, a saber, SNCA, MIF e IFNGR1. O status de metilação do DNA modif icado com bissulfito foi analisado por PCR com marcação fluorescente, eletroforese capilar e validação com sequenciamento Sanger. Resultados: Há alterações no estado de metilação do promotor dos genes MIF e SNCA nos casos. Foi observada concordância entre expressão gênica e status de metilação em MIF na amostra geral, e também com a síntese de mRNA de SNCA, sem alterações apreciáveis na proteína, embora com diferenças de acordo com o sexo. Conclusão: Nosso estudo forneceu informações sobre o estado de metilação dos promotores SNCA e MIF e sua relação com a expressão gênica em fenótipos problemáticos de consumo de álcool. Estas duas proteínas são propostas como candidatas para estudos de modelagem.
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