Association of Vitamin D Receptor Polymorphisms with Amyloid-β Transporters Expression and Risk of Mild Cognitive Impairment in a Chilean Cohort
| Autor: | Maria I. Behrens, Gonzalo A. Farías, Nohela B Arévalo, Luisa Herrera, Carolina Delgado, Daniela P Castillo-Godoy, Nicole K Rogers, Italo Espinoza-Fuenzalida, Carol D. SanMartín, Mauricio Henriquez |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Population Gene Expression Single-nucleotide polymorphism Calcitriol receptor Polymorphism Single Nucleotide RAGE (receptor) Cohort Studies 03 medical and health sciences 0302 clinical medicine Polymorphism (computer science) Risk Factors Internal medicine mental disorders Genotype medicine Vitamin D and neurology Humans Cognitive Dysfunction Taq Polymerase Chile education Aged education.field_of_study Amyloid beta-Peptides business.industry General Neuroscience Membrane Transport Proteins General Medicine LRP1 Psychiatry and Mental health Clinical Psychology 030104 developmental biology Endocrinology Receptors Calcitriol Female Geriatrics and Gerontology business 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Journal of Alzheimer's disease : JAD. 82(s1) |
| ISSN: | 1875-8908 |
| Popis: | Background: Amyloid-β peptide (Aβ) deposition in Alzheimer’s disease (AD) is due to an imbalance in its production/clearance rate. Aβ is transported across the blood-brain barrier by LRP1 and P-gp as efflux transporters and RAGE as influx transporter. Vitamin D deficit and polymorphisms of the vitamin D receptor (VDR) gene are associated with high prevalence of mild cognitive impairment (MCI) and AD. Further, vitamin D promotes the expression of LRP1 and P-gp in AD-animal model brains. Objective: To associate VDR polymorphisms Apa I (rs7975232), Taq I (rs731236), and Fok I (rs2228570) with the risk of developing MCI in a Chilean population, and to evaluate the relationship of these polymorphisms to the expression of VDR and Aβ-transporters in peripheral blood mononuclear cells (PBMCs). Methods: VDR polymorphisms Apa I, Taq I, and Fok I were determined in 128 healthy controls (HC) and 66 MCI patients. mRNA levels of VDR and Aβ-transporters were evaluated in subgroups by qPCR. Results: Alleles A of Apa I and C of Taq I were associated with a lower risk of MCI. HC with the Apa I AA genotype had higher mRNA levels of P-gp and LRP1, while the expression of VDR and RAGE were higher in MCI patients and HC. For Fok I, the TC genotype was associated with lower expression levels of Aβ-transporters in both groups. Conclusion: We propose that the response to vitamin D treatment will depend on VDR polymorphisms, being more efficient in carriers of protective alleles of Apa I polymorphism. |
| Databáze: | OpenAIRE |
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