Polymorphism Rs2421943 of the insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease.

IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Current Alzheimer research Pub Date : 2022-03-02 DOI:10.2174/1567205019666220302120950
O. Šerý, T. Zeman, Alice Hálová, V. Janout, J. Janoutová, J. Lochman, V. Balcar
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引用次数: 5

Abstract

BACKGROUND Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form β-structures. These include insulin and amyloid-β peptides. Accumulation and fibrillation of amyloid-β peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology. OBJECTIVE The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (Mild cognitive impairment) and AD. METHODS Two independent groups of 1670 patients and controls were included. The AD group consisted of 595 patients and 400 controls; the MCI group involved 135 patients and 540 matched controls. PCR and restriction fragment length analysis was used for analysis of the rs2421943 polymorphism. Using the miRBase and RNA22 prediction tools in silico indicated that the rs2421943 polymorphism is a potential target for a specific miRNA (hsa-miR-7110-5p). RESULTS AG and GG genotypes of rs2421943 significantly increased the risk of AD and the AG genotype increased the risk of MCI. It seems G allele both increases the risk of AD and accelerates the transition through the MCI phase. In silico study revealed that rs2421943 is inside the sequence binding miRNA hsa-miR-7110-5p. The polymorphism could affect the rate of IDE pre-RNA (heterogeneous nuclear RNA, hnRNA) processing, resulting in slower translation, lower levels of IDE, deficient removal of amyloid-β fragments and greater risk of and/or accelerated progression of AD. CONCLUSIONS GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulin degrading enzyme gene increase the risk of AD and MCI.
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胰岛素降解酶基因Rs2421943多态性与晚发型阿尔茨海默病的风险
背景胰岛素降解酶(IDE)是一种分布广泛的Zn2+结合金属蛋白酶,可切割多个易于形成β结构的中短肽。其中包括胰岛素和淀粉样蛋白-β肽。淀粉样蛋白-β肽的积累和纤颤导致淀粉样蛋白斑块的形成是阿尔茨海默病(AD)病理学的特征性标志。目的研究IDE基因rs2421943单核苷酸多态性(SNP)作为轻度认知障碍(MCI)和AD的危险因素。方法纳入两个独立的1670名患者和对照组。AD组包括595名患者和400名对照组;MCI组包括135名患者和540名匹配的对照组。应用聚合酶链式反应和限制性片段长度分析方法对rs2421943多态性进行分析。在计算机上使用miRBase和RNA22预测工具表明,rs2421943多态性是特定miRNA(hsa-miR-7110-5p)的潜在靶点。结果rs2421943的GG和GG基因型显著增加AD的风险,AG基因型增加MCI的风险。似乎G等位基因既增加了AD的风险,又加速了MCI期的转变。计算机研究显示rs2421943位于结合miRNA hsa-miR-7110-5p的序列内部。该多态性可能影响IDE前RNA(异质核RNA,hnRNA)处理的速率,导致翻译较慢、IDE水平较低、淀粉样蛋白-β片段去除不足以及AD进展的更大风险和/或加速。结论胰岛素降解酶基因单核苷酸多态性rs2421943的SGG和AG基因型增加了AD和MCI的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Alzheimer research
Current Alzheimer research 医学-神经科学
CiteScore
4.00
自引率
4.80%
发文量
64
审稿时长
4-8 weeks
期刊介绍: Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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