The T869C TGF beta polymorphism is associated with fracture, bone mineral density, and calcaneal quantitative ultrasound in elderly women
Faculty of Computing, Health and Science
School of Exercise, Biomedical and Health Science
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.