Association of Vitamin D Receptor Polymorphisms with Amyloid-ß Transporters Expression and Risk of Mild Cognitive Impairment in a Chilean Cohort.
J Alzheimers Dis
; 82(s1): S283-S297, 2021.
Article
em En
| MEDLINE
| ID: mdl-33216035
ABSTRACT
BACKGROUND:
Amyloid-ß peptide (Aß) deposition in Alzheimer's disease (AD) is due to an imbalance in its production/clearance rate. Aß 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 Aß-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 Aß-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 Aß-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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
/
Receptores de Calcitriol
/
Polimorfismo de Nucleotídeo Único
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Disfunção Cognitiva
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
País/Região como assunto:
America do sul
/
Chile
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Chile