Pharmacogenetics of the vitamin D receptor and osteoporosis
Osteoporosis is a major health care problem internationally with important implications for health care costs, morbidity, and mortality. Bone density, an important predictor of osteoporotic fracture risk, is affected by hormonal and environmental factors. However, in twin and family studies most of its age-specific variance is genetically determined. Common allelic variations in the vitamin D receptor (VDR) gene were the first to be linked to bone density. Recently, other candidate genes, notably oestrogen receptor, collagen 1alphaI, and PTH receptor genes and a chromosome 11 locus, have been associated with bone density and fracture. Polymorphisms in adjacent regulatory regions may be important mechanisms since functional coding region mutations have not been defined. For example, the polymorphic region in the collagen 1alphaI gene alters a SpI binding site and may alter collagen gene expression. At the pharmacogenetic level, VDR alleles predict differences in gut calcium absorption and long-term bone density response to calcium intake and active vitamin D analog treatment. Understanding the mechanisms underlying these allelic differences in relation to diet and lifestyle factors as well as response to therapy could aid selection of optimal therapy for osteoporosis prevention and treatment.
|Authors||Eisman, J. A. :|
|Publisher Name||DRUG METAB DISPOS|
|Published Date||2001-01-01 00:00:00|
|Published Issue||4 Pt 2|