O. Šerý, T. Zeman, Alice Hálová, V. Janout, J. Janoutová, J. Lochman, V. Balcar
{"title":"Polymorphism Rs2421943 of the insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease.","authors":"O. Šerý, T. Zeman, Alice Hálová, V. Janout, J. Janoutová, J. Lochman, V. Balcar","doi":"10.2174/1567205019666220302120950","DOIUrl":null,"url":null,"abstract":"BACKGROUND\nInsulin-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.\n\n\nOBJECTIVE\nThe study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (Mild cognitive impairment) and AD.\n\n\nMETHODS\nTwo 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).\n\n\nRESULTS\nAG 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.\n\n\nCONCLUSIONS\nGG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulin degrading enzyme gene increase the risk of AD and MCI.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Alzheimer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1567205019666220302120950","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
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.
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.