Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis.

Osteoporosis exhibits a substantial genetic component. Although polymorphisms of a variety of genes have been associated with bone mineral density and genetic susceptibility to osteoporosis, the genes responsible for these traits have not been definitively identified. We have shown that a T869-->C polymorphism of the transforming growth factor-beta1 gene, which results in a Leu-->Pro substitution at amino acid 10, is associated with bone mineral density in Japanese adolescents and postmenopausal women, with genetic susceptibility to both osteoporosis and vertebral fracture, and with the outcome of treatment for osteoporosis with active vitamin D. We have also shown that a C-509-->T polymorphism in the promoter region of this gene is associated with both bone mineral density and the prevalence of osteoporosis in postmenopausal women. In addition, analysis of combined genotypes for both the C-509-->T and T869-->C polymorphisms revealed that bone mineral density decreases and the susceptibility to osteoporosis increases with the number of T alleles. Thus, combined genotyping of the C-509-->T and T869-->C polymorphisms may prove beneficial in the prevention of osteoporosis in postmenopausal Japanese women. I review here the association of transforming growth factor-beta1 gene polymorphisms with genetic susceptibility to osteoporosis, which has provided insight into the function of transforming growth factor-beta1 as well as into the role of genetic factors in the development of osteoporosis.