Invited Symposium: Regulators of Skeletal Growth and Integrity in Health and Disease
Rubin, L.A. (Dept. of Medicine, Univ. of Toronto, Canada)
Geneticists consider osteoporosis to be multifactorial in origin, a concept that highlights the interactions among multiple genetic determinants and environmental effects. Twin studies reveal a substantial genetic contribution to bone mineral density (BMD), but they fail to address the evolutionary sculpting of our genetic heritage that leaves adults with sub-optimal capacity for adapting to modern changes in lifestyle and nutritional practice. One approach to the identification of the genes that predispose to osteoporosis is to explore associations with genes known to govern bone and mineral homeostasis. For the vitamin D-receptor (VDR) locus, evidence for an association of non-coding VDR polymorphisms with BMD is substantial but inconsistent. For the type I collagen gene (COL1A1), preliminary studies indicate strong associations with BMD and with fracture risk. Other promising candidates include the estrogen receptor gene, the gene for transforming growth factor-beta and perhaps biglycan. Some argue that the lack of consistent associations are evidence enough of their absence, but the likelihood that the inconsistent results reflect sampling artifact or other confounding epigenetic effects is high, especially given the large differences in polymorphic variation among different populations. Although any single polymorphism is unlikely to become a practical marker of osteoporosis predisposition, the possibility that the aggregate genetic profile will be clinically useful is not negligible, particularly when it comes to design of new preventive strategies. Many nutritional interventions in osteoporosis are currently predicated on the simplifying assumption that variability of response is due to random variation within a single homogeneous population. How much better it would be if one could predict an individual's response by defining the differences in that individual's innate ability to respond.
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|Cole, D.E.C.; Rubin, L.A.; (1998). Osteoporosis And The Interface Between Nutrition And Genetics. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/atkinson/cole0195/index.html|
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