PLos Med:糖尿病与阿尔茨海默病关联基础可能与HHEX基因有关

2015-07-15 zhaozhou 译 MedSci原创

在许多前瞻性基于人群的研究中,人们发现患有2型糖尿病的人群患痴呆和阿尔茨海默病的风险增加(如:J CLIN ENDOCR METAB:糖尿病并发症指向上升的痴呆风险)。相对于不患糖尿病的老年人,患糖尿病的老年患痴呆症风险增加50%。胰岛素降解酶(IDE)是细胞内负责清除胰岛素的酶。胰岛素代谢的变化是胰岛素抵抗的基础。编码IDE的基因位于染色体10 q23-q25,这一区域包括了IDE和HHEX。H

在许多前瞻性基于人群的研究中,人们发现患有2型糖尿病的人群患痴呆和阿尔茨海默病的风险增加(如:J CLIN ENDOCR METAB:糖尿病并发症指向上升的痴呆风险)。相对于不患糖尿病的老年人,患糖尿病的老年患痴呆症风险增加50%。胰岛素降解酶(IDE)是细胞内负责清除胰岛素的酶。胰岛素代谢的变化是胰岛素抵抗的基础。编码IDE的基因位于染色体10 q23-q25,这一区域包括了IDE和HHEX。HHEX的变异可以影响到IDE的表达。这意味着IDE/HHEX基因区域的变异是2型糖尿病和阿尔茨海默病之间有联系的基础。


为了探究IDE基因是否在二者联系中起到作用以及大脑结构的变化,研究人员使用了两个基于社群的队列以及核磁共振成像(MRI)数据。第一组包括了年龄在75岁以上且未患有痴呆的老年人,对其进行长达九年的跟踪随访来检测痴呆(n=358)和阿尔茨海默病(n=271)。第二组有2060名60岁以上的未患有痴呆症的受试者。他们被跟踪六年来确诊痴呆症和阿尔茨海默病。此外338名来自第二组的受试者接受MRI。对HHEX_23和IDE_9进行基因分型,对糖尿病进行评估。结果表明,HHEX_23和糖尿病有着相互作用。MRI数据表明有无糖尿病的携带不同HHEX_23基因的患者大脑结构变化有着显著差异。当然,MRI样本数据尚不够多。

此次研究发现HHEX_23基因和糖尿病有相互作用,HHEX突变导致患痴呆和阿尔茨海默病的风险增加。这对于筛查、预防老年性痴呆有着重要的意义。

原始出处: 

Xu W-L, Pedersen NL, Keller L, Kalpouzos G, Wang H-X, Graff C, et al. (2015) HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A PopulationBased Longitudinal Study. PLoS Med 12(7):e1001853.doi:10.1371/journal.pmed.1001853

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    2015-07-16 medcardio

    两种不同的疾病,可能有,相似的,分子机制,把它们关联起来

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