Politi Cristina, Ciccacci Cinzia, D'Amato Cinzia, Novelli Giuseppe, Borgiani Paola, Spallone Vincenza
Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Italy.
Department of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy.
Diabetes Res Clin Pract. 2016 Oct;120:198-208. doi: 10.1016/j.diabres.2016.08.006. Epub 2016 Aug 26.
Diabetic polyneuropathy and cardiovascular autonomic neuropathy are common and disabling complications of diabetes. Although glycaemic control and cardiovascular risk factors are major contributory elements in its development, diabetic neuropathy recognizes a multifactorial influence and a multiplicity of pathogenetic mechanisms. Thus genetic and environmental factors may contribute to its susceptibility, each with a modest contribution, by targeting various metabolic and microvascular pathways whose alterations intervene in diabetic neuropathy pathogenesis. This review is aimed at describing major data from the available literature regarding genetic susceptibility to diabetic neuropathies. It provides an overview of the genes reported as associated with the development or progression of these complications, i.e. ACE, MTHFR, GST, GLO1, APOE, TCF7L2, VEGF, IL-4, GPX1, eNOS, ADRA2B, GFRA2, MIR146A, MIR128A. The identification of genetic susceptibility can help in both expanding the comprehension of the pathogenetic mechanisms of diabetic nerve damage and identifying biomarkers of risk prediction and response to therapeutic intervention.
糖尿病性多发性神经病和心血管自主神经病变是糖尿病常见且致残的并发症。尽管血糖控制和心血管危险因素是其发生发展的主要促成因素,但糖尿病性神经病变受多因素影响且存在多种致病机制。因此,遗传和环境因素可能通过针对各种代谢和微血管途径影响其易感性,这些途径的改变参与了糖尿病性神经病变的发病机制,每种因素的作用相对较小。本综述旨在描述现有文献中关于糖尿病性神经病变遗传易感性的主要数据。它概述了据报道与这些并发症的发生或进展相关的基因,即血管紧张素转换酶(ACE)、亚甲基四氢叶酸还原酶(MTHFR)、谷胱甘肽S-转移酶(GST)、乙二醛酶1(GLO1)、载脂蛋白E(APOE)、转录因子7样蛋白2(TCF7L2)、血管内皮生长因子(VEGF)、白细胞介素-4(IL-4)、谷胱甘肽过氧化物酶1(GPX1)、内皮型一氧化氮合酶(eNOS)、肾上腺素能受体α2B(ADRA2B)、胶质细胞源性神经营养因子受体α2(GFRA2)、微小RNA146A(MIR146A)、微小RNA128A(MIR128A)。遗传易感性的鉴定有助于加深对糖尿病神经损伤致病机制的理解,以及识别风险预测和治疗干预反应的生物标志物。