The T869C TGF β polymorphism is associated with fracture, bone mineral density, and calcaneal quantitative ultrasound in elderly women

Osteoporosis is a disease that is strongly genetically determined and polymorphisms present in a range of candidate genes may be involved. A number of previous studies have shown an association between the T869C functional polymorphism of the gene for transforming growth factor β (TGF β) and bone mineral density (BMD) and fracture, but these studies have been limited to relatively small studies of selected subjects. In a population-based study of 1337 white women over age 70 we examined the TGF β T869 polymorphism in relation to BMD, calcaneal quantitative ultrasound (QUS), and prevalent and incident fracture. The TGF β C allele was observed in 50% of the subjects and was associated with reduced hip BMD at all sites (2.8% total hip, 2.4% femoral neck, 2.6% intertrochanter, and 3.4% trochanter) compared to the TGF β TT genotype. The TGF β C allele was also associated with a reduction in the QUS parameters BUA, SOS, and stiffness of 0.87%, 0.26%, and 2.4%, respectively, compared to the TGF β TT genotype. After adjustment for body mass index in an analysis of variance model, the effect of the TGF β C allele remained significant at the total hip, the femoral neck, and the trochanter, and for the QUS SOS and stiffness parameters. The TGF β C allele was associated with an increase in osteoporosis [T score ≤ −2.5 SD; odds ratio (OR) 2.07; 95% confidence interval (CI) 1.19–3.60] and prevalent fracture (1.37; 95% CI 1.06–1.75). After adjustment for BMD and QUS stiffness, the association of the TGF β C allele with prevalent fracture was still present (OR 1.40; 95% CI 1.04–1.89), suggesting that the effect of the C allele on fracture was independent of a reduction in BMD and QUS stiffness. Subjects with normal BMD and a TGF β C allele had an increased risk of incident fracture over 3 years compared to subjects with normal BMD and a TGF β TT genotype (relative risk 3.95; 95% CI 1.52–10.29). This association was not found in osteopenic or in osteoporotic subjects, indicating a BMD-TGF β C allele interaction in relation to the association of the TGF β C allele with fracture risk. These findings are of potential clinical usefulness, as the TGF β T869C genotype could be used, in conjunction with other genetic and clinical information, to determine an individual’s risk of osteoporosis.