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首页> 外文期刊>International Journal of Molecular Sciences >Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD)
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Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD)

机译:非酒精性脂肪肝疾病(NAFLD)的遗传和表观遗传调控

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Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3 , MBOAT7 ). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual’s susceptibility to NAFLD. Modifications of the histones amino-terminal ends are key factors in the maintenance of chromatin structure and gene expression (cAMP-responsive element binding protein H (CREBH) or SIRT1). Activation of SIRT1 showed potential against the physiological mechanisms related to NAFLD. Abnormal DNA methylation represents a starting point for cancer development in NAFLD patients. Besides, the evaluation of circulating miRNA profiles represents a promising approach to assess and non-invasively monitor liver disease severity. To date, there is no approved pharmacologic therapy for NAFLD and the current treatment remains weight loss with lifestyle modification and exercise. In this review, the status of research into relevant genetic and epigenetic modifiers of NAFLD progression will be discussed.
机译:遗传学和表观遗传学在包括非酒精性脂肪肝疾病(NAFLD)在内的几种疾病的发展中起着关键作用。家庭研究表明,NAFLD患者的一级亲属患此病的风险比普通人群高得多。基因组广泛关联研究(GWAS)技术的发展已允许鉴定涉及疾病演变的许多遗传多态性(例如PNPLA3,MBOAT7)。另一方面,表观遗传学的变化与遗传的危险因素相互作用,决定了个体对NAFLD的易感性。组蛋白氨基末端的修饰是维持染色质结构和基因表达(cAMP反应元件结合蛋白H(CREBH)或SIRT1)的关键因素。 SIRT1的激活显示出潜在的抗与NAFLD相关的生理机制的作用。 DNA甲基化异常代表了NAFLD患者癌症发展的起点。此外,循环miRNA谱的评估代表了一种有前途的评估和无创监测肝脏疾病严重程度的方法。迄今为止,尚无批准的针对NAFLD的药物疗法,目前的疗法仍然是通过改变生活方式和锻炼来减轻体重。在这篇综述中,将讨论有关NAFLD进展的相关遗传和表观遗传修饰因子的研究现状。

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