Association of transforming growth factor beta 1 genotype with therapeuticresponse to active vitamin D for postmenopausal osteoporosis

Transforming growth factor beta (TGF-P) is an important regulator of bone m etabolism, its effects being intertwined with those of estrogen and vitamin D. A T-->C polymorphism in exon 1 of the TGF-beta 1 gene, which results in the substitution of proline for leucine, is associated with bone mineral d ensity (BMD), However, it is not known whether this polymorphism affects th e response to treatment with active vitamin D or to hormone replacement the rapy (HRT) in individuals with osteoporosis. Changes in BMD at the lumbar s pine (L2-L4 BMD) were compared among TGF-beta 1 genotypes in 363 postmenopa usal Japanese women who were divided into three groups: an untreated, contr ol group (n = 130), an active vitamin D treatment group (n = 117), and an H RT group (n 116), TGF-beta 1 genotype was determined with an allele-specifi c polymerase chain reaction assay. In the control group, the rate of bone l oss decreased according to the rank order of genotypes TT (homozygous for t he T allele) > TC (heterozygous) > CC (homozygous for the C allele), with a significant difference detected between the CC and TT genotypes, The posit ive response of L2-L4 BMD to HRT increased according to the rank order of g enotypes TT < TC < CC,although the differences among genotypes were not sta tistically significant. Individuals with the CC genotype responded to activ e vitamin D treatment with an annual increase in L2-L4 BMD of 1.6%, whereas those with the TT or TC genotypes similarly treated lost bone to a similar extent as did untreated subjects of the corresponding genotype, These resu lts suggest that TGF-beta 1 genotype is associated with both the rate of bo ne loss and the response to active vitamin D treatment.