Candidate genes for osteoporosis. Therapeutic implications.
Osteoporosis, which afflicts 10 million Americans, is a complex disease characterized by decreased bone mass, microarchitectural deterioration of bone tissue, and an increase in fracture risk. Family and twin studies have established a genetic contribution to the etiology of osteoporosis. The biological candidate genes of osteoporosis can be ordered into 5 categories: (i) calcium homeostasis; (ii) hormonal dysfunction; (iii) osteoblast and osteoclast development and regulation; (vi) cartilage matrix metabolism; and (v) lipoprotein metabolism. In addition, genome-wide scans have identified a number of chromosomal regions harboring genes that influence bone mineral density. Moreover, the drug responses to various treatments of osteoporosis are reported to be modulated by DNA polymorphisms of the vitamin D receptor gene, the estrogen receptor 1 gene, and the transforming growth factor beta 1 gene. With the rapid advancement of the Human Genome Project and biotechnology, it will be possible to carry out parallel analyses of large numbers of candidate genes for osteoporosis and to calculate a patient's individual fracture risk in the context of specific environmental influences. This will eventually lead to more advanced diagnostic methods and more efficacious drugs targeting osteoporosis.
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Program for Population Genetics, Harvard School of Public Health, Boston, Massachusetts, USA. xxu@hohp.harvard.edu
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D000818:Animals; D001483:Base Sequence; D015519:Bone Density; D004247:DNA; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010024:Osteoporosis / Q000235:genetics* / Q000628:therapy*
D004247:DNA