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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2018; 76(11): 760-766
DOI: 10.1590/0004-282X20180116
Article

BsmI polymorphism in the vitamin D receptor gene is associated with 25-hydroxy vitamin D levels in individuals with cognitive decline

Polimorfismo BsmI no gene do receptor de vitamina D está associado aos níveis de 25-hidroxi vitamina D em indivíduos com declínio cognitivo

Authors

  • Ana Carolina R. de Oliveira

    1   Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Biologia Geral, Belo Horizonte MG, Brasil

  • Carolina A. Magalhães

    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil

  • Cristina M. G. Loures

    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil

  • Vanessa G. Fraga

    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil

  • Leonardo C. de Souza

    3   Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte MG, Brasil

  • Henrique C. Guimarães

    3   Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte MG, Brasil

  • Marco T. G. Cintra

    3   Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte MG, Brasil

  • Maria A. Bicalho

    3   Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte MG, Brasil

  • Maira C. R. Sousa

    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil

  • Josianne N. Silveira

    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil

  • Ieda F. O. Silva

    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil

  • Paulo Caramelli

    3   Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte MG, Brasil

  • Maria G. Carvalho

    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil

  • Karina B. Gomes

    1   Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Biologia Geral, Belo Horizonte MG, Brasil
    2   Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Análises Clínicas e Toxicológicas, Belo Horizonte MG, Brasil
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ABSTRACT

Elderly people are at a high risk of developing vitamin D (VitD) deficiency due to both decreased intake and cutaneous synthesis. Most of the biological actions of VitD are mediated by the vitamin D receptor (VDR), which is present in neurons and glial cells of the hippocampus, and in the cortex and subcortical nuclei, essential areas for cognition. It is known that VDR gene polymorphisms may decrease the VDR affinity for VitD. Objective: The present study aimed to investigate the influence of VitD levels on cognitive decline in patients with dementia due to Alzheimer's disease (AD, n = 32) and mild cognitive impairment (MCI, n = 15) compared to cognitively healthy elderly (n = 24). We also evaluated the association of VDR gene polymorphisms with cognitive disturbance. Methods: Four polymorphisms on the VDR gene were studied, namely, BsmI, ApaI, FokI and TaqI, by polymerase chain reaction-restriction fragment length polymorphism. Serum levels of 25-hydroxy vitamin D (25(OH)D) were determined by high performance liquid chromatography. Results: No significant difference in 25(OH)D levels or genotypic/allelic frequencies was observed between the groups. Deficiency of 25(OH)D was more frequently observed in women. The AA/AG genotypes of the BsmI polymorphism was associated with sufficient 25(OH)D levels, while the GG genotype of this same polymorphism was associated to insufficient levels in the cognitively-impaired group (individuals with AD or MCI). Conclusions: The data obtained do not confirm the relationship between reductions of VitD levels, polymorphisms in the VDR gene, and altered cognitive function in this sample. However, the data indicate that BsmI polymorphism in the VDR gene is associated with the VitD levels in individuals with cognitive decline.

RESUMO

Idosos apresentam risco elevado de desenvolverem deficiência de Vitamina D (VitD) devido à diminuição da ingestão e da síntese na pele. A maioria das ações biológicas da VitD é mediada pelo receptor da vitamina D (VDR), que está presente nos neurçnios e células gliais do hipocampo, e no córtex e em núcleos subcorticais, áreas essenciais para a cognição. Sabe-se que polimorfismos do gene VDR podem diminuir a afinidade do VDR pela VitD. Objetivo: O presente estudo teve como objetivo investigar a influência dos níveis de VitD no declínio cognitivo em pacientes com demência devida à doença de Alzheimer (DA, n = 32) e comprometimento cognitivo leve (CCL, n = 15) em comparação a um grupo de idosos cognitivamente saudáveis (n = 24). Nós também avaliamos a associação entre polimorfimos no gene do receptor de VitD e as alterações cognitivas. Métodos: Quatro polimorfismos no gene VDR foram estudados, sendo BsmI, ApaI, FokI e TaqI, por PCR-RFLP. Os níveis séricos de 25-hidroxi vitamina D (25(OH)D) foram determinados por HPLC. Resultados: Não houve diferença significativa nos níveis de 25(OH)D ou nas frequências genotípicas / alélicas entre os grupos. Níveis deficientes de 25(OH)D foram mais frequentes nas mulheres. Os genótipos AA / AG do polimorfismo BsmI foram associados a níveis suficientes de 25(OH)D, enquanto o genótipo GG deste mesmo polimorfismo foi associado a níveis insuficientes no grupo com comprometimento cognitivo (em indivíduos com DA ou CCL). Conclusões: Os resultados obtidos não confirmam a relação entre redução dos níveis de VitD, polimorfismos no gene VDR e função cognitiva alterada nesta amostra. No entanto, os dados indicam que o polimorfismo BsmI no gene VDR está associado aos níveis de VitD em indivíduos com declínio cognitivo.

Keywords:

Alzheimer's disease - cognitive dysfunction - vitamin D

Palavras-chave:

Doença de Alzheimer - disfunção cognitiva - vitamina D

Support

Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). LCS, PC, MGC and KBG are grateful to CNPq Research Fellowship (bolsa de produtividade em pesquisa).




Publication History

Received: 17 May 2018

Accepted: 20 July 2018

Article published online:
22 August 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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