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与2型糖尿病、遗传力差距及潜在治疗靶点相关的表观遗传修饰

Epigenetic Modifications Linked to T2D, the Heritability Gap, and Potential Therapeutic Targets.

作者信息

Szabó Monica, Máté Beáta, Csép Katalin, Benedek Theodora

机构信息

Department of Internal Medicine, University of Medicine and Pharmacy of Tîrgu Mureș, 38 Gheorghe Marinescu Street, 540139, Tîrgu Mureș, Romania.

Clinic of Internal Medicine, County Clinical Emergency Hospital of Tîrgu Mureș, 50 Gheorghe Marinescu Street, 540136, Tîrgu Mureș, Romania.

出版信息

Biochem Genet. 2018 Dec;56(6):553-574. doi: 10.1007/s10528-018-9863-8. Epub 2018 Jun 5.

Abstract

With the pandemic of type 2 diabetes (T2D), there is an ever-increasing need to fully understand the underlying mechanisms of the disease. Type 2 diabetes shows a high heritability risk (25-80%); however, genes account only for 10% of this risk. From all the risk factors for diabetes, epigenetic mechanisms have the highest statistical scoring in explaining the disease. A multitude of organ-specific epigenomic changes have been linked to type 2 diabetes. Nutritional influences, mainly in the early life, physical activity level, environmental toxins act as epigenetic factors and the recognized epigenetic changes can represent a therapeutical target, new drugs being currently in development for this application. Our current review focuses on the most common epigenetic modifications linked to type 2 diabetes or insulin resistance, the potentially emerging epigenetic-related interventions and pharmacoepigenetic knowledge.

摘要

随着2型糖尿病(T2D)的流行,全面了解该疾病的潜在机制的需求日益增加。2型糖尿病显示出较高的遗传风险(25%-80%);然而,基因仅占这种风险的10%。在所有糖尿病风险因素中,表观遗传机制在解释该疾病方面具有最高的统计得分。多种器官特异性表观基因组变化已与2型糖尿病相关联。营养影响,主要是在生命早期,身体活动水平、环境毒素作为表观遗传因素,而公认的表观遗传变化可以代表一个治疗靶点,目前正在开发针对此应用的新药。我们当前的综述重点关注与2型糖尿病或胰岛素抵抗相关的最常见表观遗传修饰、潜在出现的表观遗传相关干预措施和药物表观遗传学知识。

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