ASSOCIATION OF A POLYMORPHISM OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 GENE WITH GENETIC SUSCEPTIBILITY TO OSTEOPOROSIS IN POSTMENOPAUSAL JAPANESE WOMEN

Transforming growth factor-beta (TGF-beta) is both abundant in bone an d an important regulator of bone metabolism, A T-->C transition at nuc leotide 29 in the signal sequence region of the TGF-beta 1 gene result s in a Leu-->Pro substitution at amino acid position 10, The possible association of this polymorphism with bone mass and the prevalence of osteoporosis has now been investigated in a total of 287 postmenopausa l women from two regions (Obu City, Aichi Prefecture, and Sanda City, Hyogo Prefecture) of Japan. A significant association of TGF-beta 1 ge notype with bone mass was detected in both populations; bone mineral d ensity (BMD) at the lumbar spine was greater in individuals with the C C genotype than in those with the TT or TC genotype, The frequency of vertebral fractures was significantly lower in individuals with the CC genotype than in those with the TC or TT genotypes. For each region, multivariable logistic regression analysis revealed that the frequency of the T allele was significantly higher in subjects with osteoporosi s than in controls. Also, the serum concentration of TGF-beta 1 in ind ividuals with the CC genotype was significantly higher than that in ag e-matched subjects with the TC or TT genotype in osteoporotic or osteo penic as well as healthy control groups, These results suggest that th e T/C polymorphism of the TGF-beta 1 gene is one of the genetic determ inants of bone mass and that the T allele is an independent risk facto r for the genetic susceptibility to osteoporosis in postmenopausal Jap anese women. Thus, analysis of the TGF-beta 1 genotype may be useful i n the prevention and management of osteoporosis.