Two hereditary defects related to vitamin D metabolism map to the same region of human chromosome 12q13–14

Abstract

We have localized the locus for the vitamin D receptor (VDR) responsible for hypocalcemic vitamin D-resistant rickets (HVDRR), close to the pseudovitamin D-deficient rickets (PDDR) locus, another disorder related to impaired vitamin D metabolism. PDDR (formerly vitamin D dependency type I, VDD1) was recently mapped to human chromosome 12q14 by linkage analysis. Here we report on the assignment of VDR to 12q13-14 by in situ hybridization and by linkage analysis. Linkage analysis between VDR, PDDR, and several RFLP markers show close linkage, with no recombination (theta = 0) between VDR and PDDR (Z = 1.94), a COL2A1 haplotype (Z = 4.03), ELA1 (Z = 0.98), and D12S15 (Z = 4.17). The analysis of extended haplotypes in one of the PDDR families provides evidence for recombination between VDR and PDDR and localizes VDR together with COL2A1 proximal to PDDR. Complete allelic association detected between VDR and COL2A1 loci on PDDR chromosomes and lower association between VDR and PDDR suggests a VDR location very close to COL2A1 and one more distant to PDDR. We propose the following order of loci: (VDR, COL2A1), (PDDR, ELA1, D12S15), D12S4, (D12S14, D12S17), D12S6. Thus, two clearly distinct loci involved in the control of vitamin D activity map close to each other in the region 12q13-14.

Association between Vitamin D Receptor Gene Polymorphisms and Susceptibility to Chronic Kidney Disease and Periodontitis

“…Moreover, there is considerable scientific evidence that vitamin D has a variety of effects on immune system function that may enhance innate immunity and inhibit the development of autoimmunity [37] . Vitamin D inhibits lymphocyte proliferation and stimulates monocyte differentiation [12] , and increases secretion of cytokines, such as interleukin (IL)-2, interferon-␥ and IL-12 [38] . The vitamin D receptor is a ligand-activated transcriptional factor that mediates the effects of active vitamin D [11] in a wide variety of tissues and cells, including the heart, stomach, pancreas, brain, skin, gonads [39,40] , bone [41] and most cells of the immune system, including T cells, dendritic cells and macrophages [42] .…”

“…The human VDR is a product of a single gene, which is located on chromosome 12 at 12q13-14 [12] . The gene is comprised of 11 exons that, together with intervening introns, span approximately 75 kb [13] .…”

Role of vitamin D receptor gene Cdx2 and Apa1 polymorphisms in prostate cancer susceptibility: a meta-analysis

“…VDR is encoded by a large gene (>100 kb) mapped to chromosome 12q12-14. Its 14 exons spanning approximately 75 kb [13, 14] exhibit a high degree of polymorphism, with at least 618 reported variants, most of which are either undetectable or occur at a low frequency in the general population. Among the known VDR polymorphisms, the most common SNPs, influencing the VDR expression in prostate cancer include FokI, BsmI, ApaI, Cdx2 , and TaqI [15–18].…”

Comparative Characteristics of Rickets-Like Diseases

“…При витамин D-зависимом рахите IIA типа это приводит к нарушению связывания 1,25(OH) 2 D 3 с цитоплазматическими рецепторами клеток костей, почек, кожи и других органов и тканей, несмотря на высокий уровень данного метаболита в сыворотке крови. А при витамин D-зависимом рахите IIB типа нарушение связывания 1,25(OH) 2 D 3 с рецепторами клеток мишеней, по-видимому, обусловлено присут-ствием ядерного рибонуклеопротеина [16][17][18].…”

“…У боль-ных определяются гипокальциемия, признаки рахита или остеомаляции (вследствие недостаточной абсорбции кальция в тонком кишечнике) и наруше-ния минерализации костной ткани и хрящей. Алопе-ция, полная или частичная, является отличительным признаком данной формы заболевания, поскольку в результате мутаций в гене VDR снижается чувстви-тельность рецепторов волосяных луковиц [16,19,20].…”