Similarly to other genes polymorphisms, significant differ­ences exist in VDR polymorphisms distribution among differ­ent ethnic groups. A possible explanation to polymorphism generation phenomena is DNA damage events in an ancient small population that grow up in frequency becoming poly­morphisms in modern populations. VDR haplotypes distribu­tion reflects out-of-Africa evolution theory that describe hu­man populations origin and [...]

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Morrison and co-workers analysed an Australian population sample and evidenced the presence of association between al- lelic variants in the 3′ region (for B allele) and osteocalcin bone turnover marker levels in serum. Since 1992, several studies about correlation of VDR polymorphisms with BMD and bone turnover markers have been published, generating con­flicting data. In [...]

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Vitamin D endocrine system positively affects infection, autoim­mune diseases, tolerance in transplantation and this mainly de­rives from prodifferentiating effects on monocyte- macrophages, antigen-presenting cells, dendritic cells (DC) and lymphocytes as evidenced from in vivo and in vitro studies (Figure 4). One of the mechanisms mediating vitamin D function in resis­tance to infections is the already [...]

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Vitamin D acts in parathyroid tissue through its binding to VDR and consequent regulation of gene transcription and a VDRE was demonstrated in the promoter region of the PTH gene. Thus 1,25(OH)2D3 exerts a negative feedback on PTH production in response to PTH-dependent activation of calcium mobilization from kidney and bone, through a VDR-mediated silencing [...]

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Effects on intestinal calcium The role of vitamin D in intestinal absorption of calcium is well known and the vitamin D endocrine system has been finally identified as the agent that stimulates intestinal calcium ab­sorption to meet the needs of the skeleton (Figure 4). Ep­ithelial calcium channel TRPV6 (CaT1 or EcaC2) is necessary for calcium [...]

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Role of PTH The parathyroid gland is the calcium-sensing organ in the body and in a few seconds it responds to even slight hypocal- caemia by secreting the 84-amino acid peptide hormone PTH. Its receptor is expressed in the nephron and in osteoblasts but not in intestine and osteoclasts for example. In the kid­ney PTH [...]

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Ligand binding, involving the AF2 domain, imparts a conforma- tional change in the secondary structure of the VDR which trig­gers the recruitment of motor proteins responsible for cyto­plasmic VDR transition to the nucleus along microtubules. VDR heterodimerization with its protein partner RXR confers a conformational structure to the receptor which is critical for transactivation function [...]

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