Association of Vitamin D Receptor Polymorphisms with Amyloid-β Transporters Expression and Risk of Mild Cognitive Impairment in a Chilean Cohort
Journal
Journal of Alzheimer's Disease
ISSN
1387-2877
1875-8908
Date Issued
2021
Author(s)
Nohela B. Arévalo
Daniela P. Castillo-Godoy
Italo Espinoza-Fuenzalida
Nicole K. Rogers
Gonzalo Farias
Carolina Delgado
Mauricio Henriquez
Luisa Herrera
Carol D. SanMartín
Type
Resource Types::text::journal::journal article
Abstract
<jats:p>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.</jats:p>