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ƒZƒ~ƒi[‚Ì–Í—l(u‰‰ŽÒFZe'ev Hochberg, MD,
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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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