Avaliação dos níveis plasmáticos de vitamina D e polimorfismos no gene do seu receptor em pacientes com distúrbios cognitivos

Abstract

Vitamin D plays a role in the regulation of bone metabolism. Recently evidences suggest that it participates as an immunomodulator in various functions, and that vitamin D signaling is implicated in brain development and function. There was a change in lifestyle, with little exposure to sunlight and a low vitamin D diet, with a global hypovitaminosis D observed. The elderly are at a higher risk of developing this deficiency due to decreased cutaneous synthesis and vitamin D intake. Most of the biological actions of vitamin D are mediated by the vitamin D receptor (VDR), which is present in neurons and glial cells of the hippocampus, in the cortex and subcortical area, essential areas for cognition. VDR gene polymorphisms may decrease VDR affinity for vitamin D. Epidemiological studies have consistently demonstrated an association between lower concentrations of vitamin D and VDR gene polymorphisms with cognitive disorders, including increased risk for Alzheimer's disease (AD), a polygenic / multifactorial neurodegenerative disorder. The present study aimed to identify the influence of vitamin D on cognitive decline in patients with AD and mild cognitive impairment (MCI) compared to cognitively healthy elderly. Four polymorphisms of the VDR gene were studied: BsmI, ApaI, FokI, TaqI by PCR-RFLP technique. The serum levels of vitamin D were determined by HPLC. Genotype frequencies were compared between the groups and related to vitamin D concentrations. These results were compared between groups in a cross-sectional and longitudinal study (one year follow-up). Statistical analysis showed no significant difference in vitamin D levels or genotypic and allelic frequencies between AD, MCI and control groups. However, an association of VDR gene haplotypes with AD was observed. The allele A of the BsmI polymorphism was associated with sufficient vitamin D levels, while the GG genotype of this same polymorphism was associated to insufficient levels in individuals with AD and MCI. There was no relationship between the cognitive decline of patients with MCI and vitamin D levels in the longitudinal study. The data obtained so far did not confirm the relationship between reduction of VITD levels and polymorphisms in the VDR gene, and altered cognitive function in a small sample of the Brazilian population, under the experimental conditions of the present study, but that the BsmI polymorphism in the VDR receptor gene may be related to vitamin D levels in this population.