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The Role of VDR Gene Polymorphisms in Vitamin D Supplementation

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The vitamin D receptor (VDR) is a nuclear transcriptional regulator that activates by binding to 1a,25-dihydroxycholecalciferol (1a,25(OH)2D), known as calcitriol, which forms a heterodimer with the retinoid X receptor (RXR). Calcitriol signalling regulates various biological effects including calcium and phosphorous metabolism, parathormone secretion cell proliferation, as well as control of adaptive and innate immunity.

A T > C shift in the promoter of the VDR variant (rs11568820) removes the binding Cdx2’s transcription factor binding site just upstream of exon 1. This leads to a less pronounced protein with decreased transcriptional activity. The F allele of this variant can be found at a high rate in Asians and Europeans and at a low frequency in Sub-Saharan Africa.

The results of this research improve our understanding of how VDR gene polymorphisms alter the reaction to dietary supplements that contain calcitriol. Carriers of the TaqI and FF genotypes of the FokI polymorphisms have higher transcriptional activation and are associated with better calcium absorption, an increase in bone mineral density, and a lower risk of fractures. Further research with an unbiased design is required to increase our understanding of how these genetic variants influence vitamin D supplementation as well as its clinical significance.

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