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ƒZƒ~ƒi[‚Ì–Í—l(u‰‰ŽÒFZe'ev Hochberg, MD, PhDj

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Evolutionary perspectives of vitamin D and rickets
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Division Chief, Pediatric Endocrinology, Meyer Children's Hospital, Israel
Ze'ev Hochberg, MD, PhD

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@During postnatal growth, proliferative chondrocytes differentiate into hypertrophic chondrocytes, which subsequently undergo programmed cell death and are replaced by bone. As demonstrated by some studies, expansion of the late hypertrophic chondrocyte layer is a feature of hypophosphatemia, regardless of its mechanism. Studies in several models of rickets demonstrated that development of hypophosphatemia is associated with a parallel decrease in the number of apoptotic hypertrophic chondrocytes and expansion of the growth plate and that replacement of phosphorus prevents these changes. Parallel studies in an in vitro culture model suggest that phosphate acts directly on hypertrophic chondrocytes and promotes apoptosis in these cells.
@The current vitamin D hypothesis explains the modern distribution of human pigmentation as the result of a balance between natural selection favoring protection against folic acid destruction in areas where ultraviolet ray exposure is high, and selection for lighter pigmentation in regions far from the equator in order to facilitate vitamin D synthesis. Melanocortin 1 receptor (MC1R) gene polymorphisms influencing phenotypic variation in human skin and hair pigmentation are probably subject to this selection.
@The speaker demonstrated in his study that the rachitic children in Egypt suffer mostly from calcium insufficiency combined with vitamin D deficiency and those in Turkey from vitamin D deficiency associated with insufficient mother and child care. However, he also showed that a non-negligible percentage of controls in both countries had pure vitamin D deficiency and/or calcium insufficiency, which may suggest that other factors are involved in the pathogenesis of rickets. Although little is known about the evolutionary adaptive changes of the vitamin D receptor (VDR) genotypes, its polymorphisms may predispose to rickets in the given environment and nutrition. The Fok I (F) allele shows a tendency to be transcriptionally more efficient. In Egyptian patients, serum 1,25(OH)2D levels and 1,25(OH)2D to 25(OH)D ratio were lower in FF homozygotes, as expected to occur in subjects with a more effective VDR. Its increased prevalence may suggest an evolutionary adaptation to a vitamin D and calcium insufficient environment or lifestyle. Thus MC1R and VDR polymorphisms may have played an active role in shaping the evolutional adaptation of human distribution.
@As a consequence of recent human migrations, many individuals are now living in geographic regions with different environmental conditions than those in which their populations evolved. Because of the key role that pigmentation plays in photoprotection and vitamin D synthesis, these recent migrations have important implications for public health.

References
1. J Clin Endocrinol Metab 93:1743-1750, 2008
2. Proc Natl Acad Sci U S A 102:9637-9642, 2005
3. Yrbk Phys Anthropol 50:85-105, 2007

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