Genetics of Osteoporosis
Abstract
There is clear evidence of genetic modulation of bone phenotype parameters including bone density, quantitative ultrasound, bone size, and bone turnover. At any particular age and phase of life, genetic factors explain about 70% of the variance in bone phenotype after adjustment for major medical and disease factors. Hormonal factors, diet, and lifestyle interact with those genetic factors over time. Common allelic variation in the VDR was the first of several genes and now chromosomal loci to be implicated in the genetic determination of bone phenotype. The VDR polymorphisms have an effect weaker than originally reported, and part of the allelic effects may be mediated by effects on body size and development and even other hormonal regulators such as PTH or insulin. Irrespective of the strength or mechanism of these associations, these initial findings on the VDR stimulated the field of the genetics of osteoporosis with targeted genetic studies and now genome scan approaches. Intronic polymorphisms of the collagen I alpha 1 gene have been shown to be related to bone density and to fracture risk in several studies, although not all findings concur. Common allelic variations have now been associated with bone density for the estrogen receptor, TGF beta receptor, and TGF beta 1, for the insulin-like growth factor-I pathway, for interleukin-4 and -6 and the interleukin-1 receptor antagonist, for calcitonin and the PTH receptors and for apolipoprotein E. Of considerable…
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