Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis

Transforming growth factor (TGF)-β1 is the most abundant growth factor in human bone. It is produced by osteoblasts and inhibits osteoclast proliferation and activity and stimulates proliferation and differentiation of preosteoblasts. Several polymorphisms have been described in the TGF-β1 gene. Previously, we and others have found associations between some of these polymorphisms and bone mass. We therefore wanted to examine if these polymorphisms are also predictors of osteoporotic fractures. The polymorphisms G−1639-A, C−1348-T, C−765insC, T29-C, G74-C, 713-8delC, C788-T, and T816-20-C were examined using RFLP and sequencing in 296 osteoporotic patients with vertebral fractures and 330 normal individuals. Bone mineral density (BMD) was examined at the lumbar spine and at the femoral neck by DXA. Genotype distributions were in H-W equilibrium. Linkage disequilibrium was found between the polymorphisms. The T816-20-C genotypes were distributed differently among osteoporotic patients and normal controls. The TT genotype was less common in individuals with osteoporotic fractures (χ2 = 6.02, P< 0.05). BMD was higher in individuals with the TT-genotype (T816-20-C) at the lumbar spine, 0.960 ± 0.173 g/cm2 compared with individuals with the TC or CC genotypes: 0.849 ± 0.181 g/cm2 and 0.876 ± 0.179 g/cm2, respectively (P< 0.001, ANOVA). Similar differences between genotypes were found at the different hip regions as well as at the total hip. Individuals with the TT-genotype (C−1348-T) had higher bone mass at the femoral neck: 0.743 ± 0.134 g/cm2 compared with 0.703 ± 0.119 g/cm2 in individuals with TC or CC genotypes (P< 0.05). Individuals with the CC-genotype (T29-C) had higher bone mass at the femoral neck, 0.735 ± 0.128 g/cm2 compared with 0.703 ± 0.120 g/cm2 in individuals with TC or TT genotypes (P< 0.05) and at the total hip: 0.852 ± 0.166 g/cm2 vs. 0.818 ± 0.149 g/cm2, respectively (P< 0.05). None of the other polymorphisms were distributed differently in patients and controls and did not affect BMD. In conclusion, The TT genotype of the T816-20-C polymorphism is less common in patients with osteoporotic fractures and is associated with higher bone mass both at the lumbar spine and at the hip. The C−1348-T and T29-C polymorphisms were distributed similarly in osteoporotic patients and normal controls, however, the rare genotypes were associated with higher bone mass at the hip.