ビタミンD代謝異常症の分子栄養学的研究

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The active vitamin D, 1, 25-dihydroxyvitamin D (1, 25 (OH)_2D), expresses its function mediated through vitamin D receptor (VDR). The VDR gene is comprised of 11 exons that together with intervening introns span approximately 75 kilobases. The noncoding 5' end of the gene includes exons 1 A, 1 B, and 1C. Eight additional exons (exons 2〜9) encode the structural portion of the VDR gene product. This article reviews our contribution on pathophysiologic analysis of vitamin D-dependent rickets type II (VDDRII), the role of vitamin D (D) on phosphate metabolism, and the association of D with osteoporosis. 1) VDDR II consists of a spectrum of VDR defects is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of D analogues and calcium supplementation is usually required for the treatment, however the responses to therapy sometimes show heterogeneity. 2) Inorganic phosphate (Pi) homeostasis is maintained mainly by the regulation of sodium-dependent phosphate (Na/Pi) transporters in the renal proximal tubules. Three nonhomologous Na/Pi transporters (types I, II and III) have been identified in the renal cortex of various species. Type II Na/Pi transporters play a major role in the regulation of renal Pi reabsorption by dietary Pi and a variety of hormones including 1, 25 (OH)_2D. 3) The polymorphism at the translation initiation codon of the human VDR gene affects the bone mineral density in the lumbar spine and the extent of D-dependent transcriptional activation on 24-hydroxylase gene. These results were confirmed by various studies using different ethnic populations. From these studies, it is concluded that D and VDR system is important for bone health through the human life.
日本ビタミン学会の論文
1999-08-25

ビタミンD代謝異常症の分子栄養学的研究

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