Association of Vitamin D Receptor Polymorphisms with Amyloid-β Transporters Expression and Risk of Mild Cognitive Impairment in a Chilean Cohort.

Autor:	Arévalo NB; Center for Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile.; Programa de Genética Humana, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile., Castillo-Godoy DP; Center for Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile., Espinoza-Fuenzalida I; Center for Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile., Rogers NK; Departamento de Neurociencia, Facultad de Medicina, Universidad de Chile, Santiago, Chile., Farias G; Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile.; Centro de Investigación Clínica Avanzada (CICA), Hospital Clínico Universidad de Chile, Santiago, Chile., Delgado C; Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile., Henriquez M; Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.; Red para el Estudio de Enfermedades Cardiopulmonares de Alta Letalidad (REECPAL), Universidad de Chile, Santiago, Chile., Herrera L; Programa de Genética Humana, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile., Behrens MI; Departamento de Neurociencia, Facultad de Medicina, Universidad de Chile, Santiago, Chile.; Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile.; Centro de Investigación Clínica Avanzada (CICA), Hospital Clínico Universidad de Chile, Santiago, Chile.; Departamento de Neurología y Psiquiatría, Clínica Alemana de Santiago, Santiago, Chile., SanMartín CD; Center for Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile.; Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile.; Escuela de Tecnologia Médica, Facultad de Ciencias, Universidad Mayor, Santiago, Chile.; Escuela de Biotecnología, Facultad de Ciencias, Universidad Mayor, Santiago, Chile.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2021; Vol. 82 (s1), pp. S283-S297.
DOI:	10.3233/JAD-201031
Abstrakt:	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:	MEDLINE
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