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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F22%3A00560126" target="_blank" >RIV/67985904:_____/22:00560126 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/22:00127713

Výsledek na webu

<a href="https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=38706842811" target="_blank" >https://asep.lib.cas.cz/arl-cav/cs/csg/?repo=crepo1&key=38706842811</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1567205019666220302120950" target="_blank" >10.2174/1567205019666220302120950</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Background: Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form beta-structures. These include insulin and amyloid-beta peptides. Accumulation and fibrillation of amyloid-beta peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology.nObjective: The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (mild cognitive impairment) and AD.nMethods: 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 were used to analyze 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).nResults: AG and GG genotypes of rs2421943 significantly increased the risk of AD, and the AG genotype increased the risk of MCI. It seems the 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-beta fragments, and greater risk of and/or accelerated progression of AD.nConclusion: GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulin-degrading enzyme gene increase the risk of AD and MCI.

Název v anglickém jazyce

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

Popis výsledku anglicky

Background: Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form beta-structures. These include insulin and amyloid-beta peptides. Accumulation and fibrillation of amyloid-beta peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology.nObjective: The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (mild cognitive impairment) and AD.nMethods: 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 were used to analyze 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).nResults: AG and GG genotypes of rs2421943 significantly increased the risk of AD, and the AG genotype increased the risk of MCI. It seems the 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-beta fragments, and greater risk of and/or accelerated progression of AD.nConclusion: GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulin-degrading enzyme gene increase the risk of AD and MCI.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/NV18-04-00455" target="_blank" >NV18-04-00455: Úloha genu pro CD36 v patogenezi Alzheimerovy choroby</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Current Alzheimer Research

ISSN

1567-2050

e-ISSN

1875-5828

Svazek periodika

19

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

10

Strana od-do

236-245

Kód UT WoS článku

000836179200006

EID výsledku v databázi Scopus

2-s2.0-85128634714