Resistance to vitamin D has been known for decades as vitamin D resistant rickets, caused by mutations of the gene encoding for vitamin D receptor (VDR). Findings of extra-skeletal effects of vitamin D and learning of the molecular mechanisms used by its biologically active metabolite calcitriol revealed other ways leading to its impaired sensitivity. Calcitriol takes advantage of both genomic and non-genomic mechanisms through its binding to vitamin D receptor, located not only in the cell nuclei but also in a perinuclear space. On the genomic level the complex of calcitriol bound to VDR binds to the DNA responsive elements of the controlled gene in concert with another nuclear receptor, retinoid X receptor, and expression of the VDR itself is controlled by its own ligand. These elements were found not only in the promotor region, but are scattered over the gene DNA. The gene expression includes a number of nuclear transcription factors which interact with the responsive elements and with each other and learning how they operate would further contribute to revealing causes of the impaired vitamin D sensitivity. Finally, the examples of major disorders are provided, associated with impairment of the vitamin D function and its receptor.
- MeSH
- kalcitriol genetika metabolismus MeSH
- lidé MeSH
- mutace genetika MeSH
- nedostatek vitaminu D farmakoterapie genetika metabolismus MeSH
- receptory kalcitriolu genetika metabolismus MeSH
- vitamin D aplikace a dávkování genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kalcitriol MeSH
- receptory kalcitriolu MeSH
- VDR protein, human MeSH Prohlížeč
- vitamin D MeSH
BACKGROUND: The low-density lipoprotein receptor-related protein 5 (LRP5) gene has been recently identified as a novel candidate for osteoporosis. The c.4037C>T polymorphism in the LRP5 gene has been associated with bone mass variance in general population. In contrast, the IVS8+443G>A polymorphism in the vitamin D receptor gene (VDR) has not been investigated in relation to bone metabolism. The aim of the present study was to determine VDR IVS8+443G>A and LRP5 c.4037C>T polymorphisms in a cohort of 165 perimenopausal women and to associate the genotypes with biochemical and densitometric bone parameters in a subset of 112 postmenopausal women. METHODS: Both polymorphisms were assessed by restriction analysis of the PCR product. Calcium, parathyroid hormone, vitamin D metabolites and bone mineral density (BMD, g/cm(2)) at the hip and in the spine (L(1)-L(4)) were examined. RESULTS: The genotype frequencies of both IVS8+443G>A (UU 75.2%, Uu 23%, uu 1.8%) and c.4037C>T (CC 73.9% TC 23.6%, TT 2.4%) were comparable to other Caucasian female cohorts. Serum 25OH vitamin D levels, assessed in only 63 probands, were significantly associated with VDR genotypes (ANCOVA, p
- MeSH
- genotyp MeSH
- kostní denzita genetika fyziologie MeSH
- kyčel diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- menopauza krev genetika metabolismus MeSH
- páteř diagnostické zobrazování MeSH
- polymorfismus genetický * MeSH
- postmenopauzální osteoporóza etnologie genetika patofyziologie MeSH
- proteiny související s LDL-receptory genetika metabolismus MeSH
- receptory kalcitriolu genetika metabolismus MeSH
- rentgendiagnostika MeSH
- senioři MeSH
- vitamin D krev genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- proteiny související s LDL-receptory MeSH
- receptory kalcitriolu MeSH
- vitamin D MeSH
- MeSH
- alfa-globuliny analýza genetika MeSH
- fenotyp MeSH
- lidé MeSH
- protein vázající vitamin D MeSH
- rodokmen MeSH
- transportní proteiny analýza genetika MeSH
- vitamin D analýza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- alfa-globuliny MeSH
- protein vázající vitamin D MeSH
- transportní proteiny MeSH
- vitamin D MeSH
