Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics
David Vogrinc,
Sara Redenšek Trampuž,
Tanja Blagus,
Maja Trošt,
Milica Gregorič Kramberger,
Andreja Emeršič,
Saša Čučnik,
Katja Goričar,
Vita Dolžan
Affiliations
David Vogrinc
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia
Sara Redenšek Trampuž
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia
Tanja Blagus
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia
Maja Trošt
Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia
Milica Gregorič Kramberger
Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia; Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Alfred Nobels allé 23, 141 52, Huddinge, Sweden
Andreja Emeršič
Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, Ljubljana, Slovenia
Saša Čučnik
Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, Ljubljana, Slovenia; Department of Rheumatology, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia; Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia
Katja Goričar
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia
Vita Dolžan
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia
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 Aβ42/40 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.
