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Open Access Research article

Transforming growth factor beta-1 (TGFB1) and peak bone mass: association between intragenic polymorphisms and quantitative ultrasound of the heel

Peter Tzakas1, Betty YL Wong2, Alexander G Logan34, Laurence A Rubin45 and David EC Cole1246*

Author Affiliations

1 Dept. of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, Canada

2 Dept. of Clinical Pathology, Sunnybrook and Women's College Health Sciences Centre, Toronto ON, Canada

3 Prosserman Centre for Health Research, Mount Sinai Hospital, Toronto ON, Canada

4 Dept. of Medicine, University of Toronto, Toronto ON, Canada

5 Dept. of Rheumatology, St Michael's Hospital, Toronto ON, Canada

6 Dept. of Paediatrics (Genetics), University of Toronto, Toronto ON, Canada

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BMC Musculoskeletal Disorders 2005, 6:29  doi:10.1186/1471-2474-6-29

Published: 14 June 2005



Variance of peak bone mass has a substantial genetic component, as has been shown with twin studies examining quantitative measures such as bone mineral density (BMD) and quantitative ultrasound (QUS). Evidence implicating single nucleotide polymorphisms (SNPs) of the transforming growth factor beta-1 (TGFB1) gene is steadily accumulating. However, a comprehensive look at multiple SNPs at this locus for their association with indices of peak bone mass has not been reported.


A cohort of 653 healthy Caucasian females 18 to 35 years old was genotyped for seven TGFB1 SNPs. Polymorphisms were detected by restriction endonuclease digestion of amplified DNA segments.


The frequencies of the least common allele at G-800A, C-509T, codon 10 (L10P), codon 25 (R25P), codon 263 (T263I), C861-20T, and 713-8 delC loci were 0.07, 0.33, 0.41, 0.08, 0.04, 0.25 and 0.01, respectively. A significant association was seen between QUS Stiffness Index (QUS-SI) and the SNP at codon 10 and the linked promoter SNP, C-509T. This association remained significant after multiple regression was used to incorporate important clinical covariates – age, BMI, level of activity, family history, and caffeine intake – into the model.


The association of QUS-SI with -509T is consistent with a gene-dose effect, while only individuals homozygous for the codon 10P allele showed a significant increase. In this cohort of young healthy Caucasian females, the T allele at position -509 is associated with greater bone mass as measured by calcaneal ultrasound.