Genetic contributions play an important role in determining bone mineral density (BMD) and bone turnover. Transforming growth factor-beta (TGF-beta) is abundant in bone and has been implicated as an important regulator of both bone formation and resorption. Several polymorphisms of the TGF-beta1 gene have recently been suggested to be associated with BMD and susceptibility to osteoporotic spine fractures. To determine the relationship between TGF-beta1 polymorphisms and BMD in southern Chinese women, three SNPs at C(-1348) -T, T29 -C, and T(861-20) -C of TGF-beta1 gene were analyzed in 237 postmenopausal southern Chinese women by RFLP and direct sequencing. BMD at the lumbar spine and hip region, biochemical markers of bone turnover, as well as serum levels of TGF-beta1 were measured. Only the T29 -C polymorphism of TGF-beta1 gene was associated with BMD and fracture risk. The prevalence of fragility fractures was significantly higher in individuals with TC genotype (P < 0.05). Serum alkaline phosphatase and osteocalcin levels as well as urinary N-telopeptide excretion were significantly higher in women with TC than with TT or CC genotypes, and the difference remained significant after adjusting for age and BMI (all P < 0.05). Women with TC genotype had lower BMD at the trochanteric (P < 0.03) and total hip region (P = 0.05). No difference was observed in the serum TGF-beta1 levels among the three genotypes. In conclusion, an association between T29 -C polymorphisms of TGF-beta1 gene and BMD, bone turnover as well as fragility fractures were demonstrated in postmenopausal southern Chinese women.