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Keywords:

  • TGF-β;
  • gene polymorphism;
  • osteoporosis;
  • active vitamin D;
  • hormone replacement therapy

Abstract

Transforming growth factor β (TGF-β) is an important regulator of bone metabolism, its effects being intertwined with those of estrogen and vitamin D. A T[RIGHTWARDS ARROW]C polymorphism in exon 1 of the TGF-β1 gene, which results in the substitution of proline for leucine, is associated with bone mineral density (BMD). However, it is not known whether this polymorphism affects the response to treatment with active vitamin D or to hormone replacement therapy (HRT) in individuals with osteoporosis. Changes in BMD at the lumbar spine (L2–L4 BMD) were compared among TGF-β1 genotypes in 363 postmenopausal Japanese women who were divided into three groups: an untreated, control group (n = 130), an active vitamin D treatment group (n = 117), and an HRT group (n = 116). TGF-β1 genotype was determined with an allele-specific polymerase chain reaction assay. In the control group, the rate of bone loss decreased according to the rank order of genotypes TT (homozygous for the T allele) > TC (heterozygous) > CC (homozygous for the C allele), with a significant difference detected between the CC and TT genotypes. The positive response of L2–L4 BMD to HRT increased according to the rank order of genotypes TT < TC < CC, although the differences among genotypes were not statistically significant. Individuals with the CC genotype responded to active 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 results suggest that TGF-β1 genotype is associated with both the rate of bone loss and the response to active vitamin D treatment.