VDR Gene Single Nucleotide Polymorphisms and Autoimmunity: A Narrative Review

Abstract

The vitamin D/Vitamin D receptor (VDR) axis is crucial for human health as it regulates the expression of genes involved in different functions, including calcium homeostasis, energy metabolism, cell growth and differentiation, and immune responses. In particular, the vitamin D/VDR complex regulates genes of both innate and adaptive immunity. Autoimmune diseases are believed to arise from a genetic predisposition and the presence of triggers such as hormones and environmental factors. Among these, a role for Vitamin D and molecules correlated to its functions has been repeatedly suggested. Four single nucleotide polymorphisms (SNPs) of the VDR gene, ApaI, BsmI, TaqI, and FokI, in particular, have been associated with autoimmune disorders. The presence of particular VDR SNP alleles and genotypes, thus, was observed to modulate the likelihood of developing diverse autoimmune conditions, either increasing or reducing it. In this work, we will review the scientific literature suggesting a role for these different factors in the pathogenesis of autoimmune conditions and summarize evidence indicating a possible VDR SNP involvement in the onset of these diseases. A better understanding of the role of the molecular mechanisms linking Vitamin D/VDR and autoimmunity might be extremely useful in designing novel therapeutic avenues for these disorders.

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

“…Vitamin D, a pivotal regulator of immune responses, influences various mechanisms. Polymorphisms in the vitamin D receptor (VDR) gene are linked to autoimmunity and an increased risk of infectious diseases [ 102 ], particularly affecting human intestinal T cells and enhancing type 1 immune responses. Vitamin D impacts the differentiation and maintenance of Treg and TH17 cells, crucial for immune response control and implicated in autoimmunity [ 103 ].…”

“…The generation of Treg cells is promoted by diet-derived SCFAs like butyrate, influenced by the microbiota [ 104 , 105 ]. Vitamin D also interacts with AhR, involved in mediating IL-22 expression and antimicrobial control in animal models [ 102 ]. Overexpressed in various tumors, AhR plays a key role in cancer development and the immune response, making it a promising therapeutic target [ 106 , 107 ].…”

Modulation of the Gut Microbiota by Nutrition and Its Relationship to Epigenetics

“…It is believed that vitamin D may play an important role in the occurrence and development of autoimmune diseases, and the presence of specific alleles and genotypes of a single VDR nucleotide modulates their development. Moreover, the vitamin D/VDR axis regulates the expression of genes involved in various functions [97], including: The vitamin D/VDR axis is largely influenced by environmental factors such as diet and sun exposure [97]. In addition to the previously mentioned important role of VDR in immune response, it is also responsible for regulating the inflammatory response and maintaining intestinal homeostasis [98].…”

Prevalence and effects of Vitamin D receptor polymorphism on bone mineral density and metabolism in patients with systemic sclerosis: a preliminary study

“…The VDR has high a nity for calcitriol and is responsible for its hormonal effects as a ligand-activated transcription factor (14). Based on single nucleotide polymorphisms more than 900 allelic variants of the VDR gene are known, that can result in lower binding qualities of the receptor for calcitriol, which subsequently leads to alterations in vitamin D and calcium metabolism (14,15). More importantly, speci c length polymorphisms of restriction fragments could be found that in uence BMD, particularly in patients with in ammatory rheumatic joint diseases (16).…”