Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics

Vogrinc, David (author), Redenšek Trampuž, Sara (author), Blagus, Tanja (author), Trošt, Maja (author), Gregorič Kramberger, Milica (author), Emeršič, Andreja (author), Čučnik, Saša (author), Goričar, Katja (author), Dolžan, Vita (author)

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Their treatment options are rather limited, and no neuroprotective or disease-modifying treatments are available. Anti-diabetic drugs, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonists, have been suggested as a potential therapeutic option. Aims: Assess GLP1R and GIPR genetic variability in relation to AD- and PD-related phenotypes. Methods: AD, PD patients and healthy control subjects were included in the study. Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease were measured in AD patients, while cognitive impairment was evaluated in PD. All participants were genotyped for three SNPs: GLP1R rs10305420, GLP1R rs6923761 and GIPR rs1800437. Results: GLP1R rs10305420 genotypes were associated with increased odds for AD and PD development. GLP1R rs10305420 and GLP1R rs6923761 genotypes were significantly associated with Aβ$_{42/40}$ ratio (p = 0.041 and p = 0.050), while GLP1R rs6923761 was also associated with p-tau levels (p = 0.022). Finally, GIPR rs1800437 heterozygotes as well as carriers of at least one GIPR rs1800437 C allele presented with increased odds for the development of dementia in PD (OR = 1.92; 95 % CI = 1.05-3.51; p = 0.034 and OR = 1.95; 95 % CI = 1.08-3.52; p = 0.027, respectively). Conclusion: GLP1R and GIPR genetic variability may affect the occurrence of AD and PD and is also associated with AD CSF biomarkers for Alzheimer's disease and dementia in PD. The data on GLP1R and GIPR genetic variability may support the function of incretin receptors in neurodegeneration.

• Language: English
• Keywords: Alzheimer's disease, biomarker, glucagon-like peptide 1 receptor, glucose-dependent insulinotropic polypeptide, Parkinson's disease, polymorphism
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 9 str.
• Numbering: Vol. 10, iss. 20, art. e39157
• PID: 20.500.12556/RUL-169763
• UDC: 616.8:577
• ISSN on article: 2405-8440
• DOI: 10.1016/j.heliyon.2024.e39157
• COBISS.SI-ID: 214994947
• Publication date in RUL: 09.06.2025

Record is a part of a journal

• Title: Heliyon
• Publisher: Elsevier
• ISSN: 2405-8440
• COBISS.SI-ID: 21607432

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: Alzheimerjeva bolezen, biološki označevalec, glukagonu podoben receptor peptid 1, od glukoze odvisen insulinotropni polipeptid, Parkinsonova bolezen, polimorfizem

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku