PREDICTION OF BONE-DENSITY FROM VITAMIN-D RECEPTOR ALLELES

BONE density achieved in early adulthood is the major determinant of r isk of osteoporotic fracture. Up to 60% of women1,2 suffer osteoporoti c fractures as a result of low bone density2, which is under strong ge netic control-3-6 acting through effects on bone turnover 7, 8. Here w e show that common allelic variants in the gene encoding the vitamin D receptor9 can be used to predict differences in bone density, account ing for up to 75% of the total genetic effect on bone density in healt hy individuals. The genotype associated with lower bone density was ov errepresented in postmenopausal women with bone densities more than 2 standard deviations below values in young normal women. The molecular mechanisms by which bone density is regulated by the vitamin D recepto r gene are not certain, although allelic differences in the 3' untrans lated region may alter messenger RNA levels. These findings could open new avenues to the development and targeting of prophylactic interven tions. It follows that other pathophysiological processes considered t o be subject to complex multifactorial genetic regulation may also be modulated by a single gene with pleiotropic transcriptional actions.