ABSTRACT
RESUMEN: El alcoholismo es una enfermedad crónica recidivante asociada a disfunción psicológica, social y física. El alcohol no sólo es una droga adictiva, también produce alteraciones en las actividades y funciones de múltiples sistemas y órganos. Actualmente, diversos estudios demuestran que el ambiente puede modular la expresión génica del ADN mediante mecanismos epigenéticos, sugiriendo de esta manera, que el consumo de alcohol es un factor que puede alterar los patrones epigenéticos y, por lo tanto, los niveles de expresión génica. La metilación del ADN es un proceso epigenético que participa en la regulación de la expresión génica, impidiendo la unión de factores de transcripción y propiciando la estructura cerrada de la cromatina. En este sentido, los cambios en la metilación del ADN se reconocen como una de las formas más comunes de alteración molecular en la dependencia al alcohol y los procesos neoplásicos humanos. El alcohol puede ser un factor importante en la iniciación del cáncer, aumentando la expresión de ciertos oncogenes o reprimiendo la capacidad de las células para reparar el ADN, lo que aumenta la probabilidad de que se produzcan mutaciones oncogénicas. Sin embargo, los mecanismos exactos de la patogénesis del cáncer ligada al consumo de alcohol aún permanecen sin ser dilucidados. Por lo anterior, el objetivo de la presente revisión fue describir los mecanismos de metilación del ADN y su relación con el consumo de alcohol y cáncer.
SUMMARY: Alcoholism is a chronic relapsing disease associated with psychological, social and physical dysfunction. Alcohol is not only an addictive substance, it also alters action and function of multiple systems and organs. Currently, several studies show that the environment can modulate gene expression of DNA by epigenetic mechanisms, thereby suggesting that alcohol consumption is a factor that can alter epigenetic patterns and therefore, the levels of gene expression. DNA methylation is an epigenetic process, that is a part of gene expression regulation preventing binding of transcription factors and encouraging the closed structure of chromatin. In this sense, changes in DNA methylation are recognized as one of the most common forms of molecular alteration in alcohol dependence and human neoplastic processes. Alcohol can be an important factor in activating the cancer by increasing the expression of certain oncogenes or repressing the ability of cells to repair DNA, which increases the likelihood of oncogenic mutations. However, the exact mechanisms of the pathogenesis of cancer linked to alcohol consumption remain unclear. Therefore, the objective of this review was to describe the mechanisms of DNA methylation and its relation to alcohol consumption and cancer.
Subject(s)
Humans , Alcohol Drinking/adverse effects , DNA Methylation/drug effects , Epigenesis, Genetic/drug effects , Neoplasms/chemically induced , Ethanol/adverse effects , Alcoholism , Carcinogenesis/chemically induced , Neoplasms/geneticsABSTRACT
Fundamentos: O nível de metilação global do ADN de leucócitos no sangue tem sido associado ao risco de doença arterial coronariana (DAC), com resultados inconsistentes em diferentes populações. Faltam dados semelhantes da população chinesa, onde diferentes fatores genéticos, de estilo de vida e ambientais podem afetar a metilação do ADN e sua relação com o risco de DCC. Objetivos: Analisar se a metilação global está associada ao risco de doença coronariana na população chinesa. Métodos: Foram incluídos um total de 334 casos de DCC e 788 controles saudáveis. A metilação global do ADN de leucócitos de sangue foi estimada por meio da análise das repetições do LINE-1 usando pirosequenciamento de bissulfito. Resultados: Em uma análise inicial restrita aos controles o nível do LINE-1 diminui significativamente com a idade avançada, colesterol total elevado, e diagnóstico de diabetes. Na análise de caso-controle, a redução da metilação do LINE-1 foi associada ao aumento do risco de DCC, tendo a análise por quartil revelado uma odds ratio (IC 95%) de 0,9 (0,6-1,4), 1,9 (1,3-2,9) e 2,3 (1,6 3.5) para o terceiro, segundo e primeiro (o mais baixo) quartil (P da tendência < 0,001), respectivamente, em comparação com o quarto (o mais alto) quartil. A metilação inferior (< mediana) do LINE-1 esteve associada a 2,2 vezes (IC 95% = 1,7-3,0) o aumento de risco de doença coronariana. As estimativas de risco de DCC menores relacionadas com o LINE-1 tenderam a ser mais fortes entre os indivíduos com maior tercil de homocisteína (P interação = 0,042) e naqueles com diagnóstico de hipertensão arterial (P interação = 0,012). Conclusão: A hipometilação do LINE-1 está ...
Background: Global methylation level in blood leukocyte DNA has been associated with the risk of coronary heart disease (CHD), with inconsistent results in various populations. Similar data are lacking in Chinese population where different genetic, lifestyle and environmental factors may affect DNA methylation and its risk relationship with CHD. Objectives: To examine whether global methylation is associated with the risk of CHD in Chinese population. Methods: A total of 334 cases with CHD and 788 healthy controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats using bisulfite pyrosequencing. Results: In an initial analysis restricted to control subjects, LINE-1 level reduced significantly with aging, elevated total cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced LINE-1 methylation was associated with increased risk of CHD; analysis by quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3 (1.6-3.5) for the third, second and first (lowest) quartile (Ptrend < 0.001), respectively, compared to the fourth (highest) quartile. Lower (<median) LINE-1 methylation was associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among subjects with the highest tertile of homocysteine (Pinteraction = 0.042) and those with diagnosis of hypertension (Pinteraction = 0.012). Conclusion: LINE-1 hypomethylation is associated with the risk of CHD in Chinese population. Potential CHD risk factors such as older age, elevated total cholesterol, and diagnosis of diabetes may have impact on global DNA methylation, whereby exerting their effect on CHD risk. .