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2 型糖尿病的药物基因组表观遗传学:它具有临床相关性吗?

Pharmacoepigenetics in type 2 diabetes: is it clinically relevant?

机构信息

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.

出版信息

Diabetologia. 2022 Nov;65(11):1849-1853. doi: 10.1007/s00125-022-05681-x. Epub 2022 Mar 21.

Abstract

Data generated over nearly two decades clearly demonstrate the importance of epigenetic modifications and mechanisms in the pathogenesis of type 2 diabetes. However, the role of pharmacoepigenetics in type 2 diabetes is less well established. The field of pharmacoepigenetics covers epigenetic biomarkers that predict response to therapy, therapy-induced epigenetic alterations as well as epigenetic therapies including inhibitors of epigenetic enzymes. Not all individuals with type 2 diabetes respond to glucose-lowering therapies in the same way, and there is therefore a need for clinically useful biomarkers that discriminate responders from non-responders. Blood-based epigenetic biomarkers may be useful for this purpose. There is also a need for a better understanding of whether existing glucose-lowering therapies exert their function partly through therapy-induced epigenetic alterations. Finally, epigenetic enzymes may be drug targets for type 2 diabetes. Here, I discuss whether pharmacoepigenetics is clinically relevant for type 2 diabetes based on studies addressing this topic.

摘要

近二十年来的数据清楚地表明,表观遗传修饰和机制在 2 型糖尿病的发病机制中非常重要。然而,药物遗传学在 2 型糖尿病中的作用还没有得到很好的证实。药物遗传学领域涵盖了预测治疗反应的表观遗传生物标志物、治疗诱导的表观遗传改变以及包括表观遗传酶抑制剂在内的表观遗传治疗。并非所有 2 型糖尿病患者对降糖治疗的反应都相同,因此需要有临床有用的生物标志物来区分应答者和无应答者。基于血液的表观遗传生物标志物可能对此有用。还需要更好地了解现有的降糖治疗是否通过治疗诱导的表观遗传改变来发挥其作用。最后,表观遗传酶可能是 2 型糖尿病的药物靶点。在这里,我根据研究该主题的研究讨论了药物遗传学在 2 型糖尿病中的临床相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dccb/9522755/28c83bf61b2e/125_2022_5681_Fig1_HTML.jpg

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