Skip to main content
SpringerLink
Log in

Transforming Growth Factor-β1 Gene Polymorphisms and Bone Turnover, Bone Mineral Density and Fracture Risk in Southern Chinese Women

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Genetic contributions play an important role in determining bone mineral density (BMD) and bone turnover. Transforming growth factor-β (TGF-β) is abundant in bone and has been implicated as an important regulator of both bone formation and resorption. Several polymorphisms of the TGF-β1 gene have recently been suggested to be associated with BMD and susceptibility to osteoporotic spine fractures. To determine the relationship between TGF-β1 polymorphisms and BMD in southern Chinese women, three SNPs at C−1348-T, T29-C, and T861-20-C of TGF-β1 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-β1 were measured. Only the T29-C polymorphism of TGF-β1 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-β1 levels among the three genotypes. In conclusion, an association between T29-C polymorphisms of TGF-β1 gene and BMD, bone turnover as well as fragility fractures were demonstrated in postmenopausal southern Chinese women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. JA Kanis LJ Melton SuffixIII C Christiansen CC Johnston N Khaltaev (1994) ArticleTitleThe diagnosis of osteoporosis. J Bone Miner Res 9 1137–1141 Occurrence Handle1:STN:280:ByqD28jgtFY%3D Occurrence Handle7976495

    CAS  PubMed  Google Scholar 

  2. NA Pock JA Eisman JL Hopper MG Yeates PN Sambrook S Eberl (1987) ArticleTitleGenetic determinants of bone mass in adults: a twin study. J Clin Invest 80 706–710 Occurrence Handle1:STN:280:BiiA3cfotVM%3D Occurrence Handle3624485

    CAS  PubMed  Google Scholar 

  3. R Gueguen P Jouanny F Guillemin C Kuntz J Poure G Siest (1995) ArticleTitleSegregation analysis and variance components analysis on bone mineral density in healthy families. J Bone Miner Res 12 2017–2022

    Google Scholar 

  4. S Ferrari R Rizzoli T Chevalley D Slosman JA Eisman JP Bonjour (1995) ArticleTitleVitamin D-receptor-gene polymorphisms and change in lumbar spine bone mineral density. Lancet 345 423–424 Occurrence Handle10.1016/S0140-6736(95)90404-2 Occurrence Handle1:STN:280:ByqC2MjgslU%3D Occurrence Handle7853953

    Article  CAS  PubMed  Google Scholar 

  5. AWC Kung SCC Yeung KS Lau (1998) ArticleTitleVitamin D receptor gene polymorphisms and peak bone mass in southern Chinese women. Bone 22 389–393 Occurrence Handle10.1016/S8756-3282(97)00301-3 Occurrence Handle1:STN:280:DyaK1c3hsFChtQ%3D%3D Occurrence Handle9556140

    Article  CAS  PubMed  Google Scholar 

  6. SFA Grant DM Reid G Blake R Herd I Fogelman SH Ralston (1996) ArticleTitleReduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type Iα1 gene. Nature Genetics 14 203–205 Occurrence Handle1:CAS:528:DyaK28XmtVKntb4%3D Occurrence Handle8841196

    CAS  PubMed  Google Scholar 

  7. BL Langdahl E Lokke M Caaarsten LL Stenkjaer EFA Eriksen (2000) ArticleTitleTA repeat polymorphism in the estrogen receptor gene is associated with osteoporotic fractures but polymorphisms in the first exon and intron are not. J Bone Miner Res 15 2222–2230 Occurrence Handle1:CAS:528:DC%2BD3cXnvVKltLo%3D Occurrence Handle11092403

    CAS  PubMed  Google Scholar 

  8. AYY Ho SSC Yeung AWC Kung (2000) ArticleTitlePvuII polymorphisms of the estrogen receptor α and bone mineral density in healthy southern Chinese women. Calcif Tissue Int 66 405–408 Occurrence Handle10.1007/s002230010082 Occurrence Handle1:CAS:528:DC%2BD3cXksVSjsLw%3D Occurrence Handle10821874

    Article  CAS  PubMed  Google Scholar 

  9. HH Lau AYY Ho KDK Luk AWC Kung (2002) ArticleTitleEstrogen receptor β gene polymorphisms are associated with higher bone mineral density in premenopausal, but not postmenopausal, southern Chinese women. Bone 31 276–281 Occurrence Handle10.1016/S8756-3282(02)00827-X Occurrence Handle1:CAS:528:DC%2BD38XlvVWgtL4%3D Occurrence Handle12151079

    Article  CAS  PubMed  Google Scholar 

  10. RE Murray F McGuigan SF Grant DM Reid SH Ralston (1997) ArticleTitlePolymorphisms of the interleukin-6 gene are associated with bone mineral density. Bone 21 89–92 Occurrence Handle10.1016/S8756-3282(97)00081-1 Occurrence Handle1:CAS:528:DyaK2sXkslamsbs%3D Occurrence Handle9213013

    Article  CAS  PubMed  Google Scholar 

  11. L Masi L Becheini L Gennari E Colli R Mansani A Falchetti C Cepollaro S Gonnelli A Tanini ML Brandi (1998) ArticleTitleAllelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women. Biochem Biophys Res Commun 245 IssueID2 622–626 Occurrence Handle10.1006/bbrc.1998.8445 Occurrence Handle1:CAS:528:DyaK1cXivVyju7g%3D Occurrence Handle9571205

    Article  CAS  PubMed  Google Scholar 

  12. BL Langdahl M Carstens L Atenkjaer EF Eriksen (2002) ArticleTitlePolymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res 16 1245–1255

    Google Scholar 

  13. J Pfeilschifter SM D’Souza GR Mundy (1987) ArticleTitleEffects of transforming growth factor beta-β on osteoblastic osteosarcoma cells. Endocrinology 121 212–218 Occurrence Handle1:CAS:528:DyaL2sXksFaqtLg%3D Occurrence Handle3474142

    CAS  PubMed  Google Scholar 

  14. C Chenu J Pfeilschifter GR Mundy GD Roodman (1988) ArticleTitleTransforming growth factor beta β inhibits formation of osteoclast-like cells in long-term human marrow cultures. Proc Natl Acad Sci USA 85 5683–5687 Occurrence Handle1:CAS:528:DyaL1cXkvVKqu7Y%3D Occurrence Handle3165196

    CAS  PubMed  Google Scholar 

  15. LF Bonewald GR Mundy (1990) ArticleTitleRole of transforming growth factor-beta in bone remodeling. Clin Orthop 250 261–276 Occurrence Handle2403492

    PubMed  Google Scholar 

  16. R Pacifici (1991) ArticleTitleEstrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 11 1043–1051

    Google Scholar 

  17. MJ Oursler C Cortese P Keeting MA Anderson SK Bonde BL Riggs TC Spelsberg (1991) ArticleTitleModulation of transforming growth factor-β production in normal human osteoblast-like cells by 17β-estradiol and parathyroid hormone. Endocrinology 129 3313–3320 Occurrence Handle1:CAS:528:DyaK38Xns1Grtw%3D%3D Occurrence Handle1954907

    CAS  PubMed  Google Scholar 

  18. GR Mundy LF Bonewald (1992) Transforming growth factor beta. M Gowen (Eds) Cytokines and bone metabolism. CRC Boca Raton, FL 93–107

    Google Scholar 

  19. K Janssens R Gershoni-Baruch N Guanabens et al. (2000) ArticleTitleMutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease. Nat Genet 26 273–275 Occurrence Handle10.1038/81563 Occurrence Handle1:CAS:528:DC%2BD3cXotVWhsL0%3D Occurrence Handle11062463

    Article  CAS  PubMed  Google Scholar 

  20. Y Yamada A Miyauchi J Goto Y Takagi H Okuizumi M Kanematsu M Hase H Takai A Harada K Ikeda (1998) ArticleTitleAssociation of a polymorphism of the transforming growth factor-β1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res 13 1569–1575 Occurrence Handle1:CAS:528:DyaK1cXntFGru7g%3D Occurrence Handle9783545

    CAS  PubMed  Google Scholar 

  21. Y Yamada A Miyauchi M Takaka M Mizuno A Harada (2001) ArticleTitleAssociation of the C-509→T polymorphism, alone or in combination with the T869→C polymorphism, of the transforming growth factor-β1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J Mol Med 79 149–156 Occurrence Handle10.1007/s001090100190 Occurrence Handle1:CAS:528:DC%2BD3MXjvVOhsr4%3D Occurrence Handle11357939

    Article  CAS  PubMed  Google Scholar 

  22. BL Langdhl JY Knudsen HK Jensen N Gregersen EF Eriksen (1997) ArticleTitleA sequence variation: 713-8delC in the transforming growth factor-beta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass and increased bone turnover in both osteoporotic and normal women. Bone 20 IssueID3 289–294 Occurrence Handle1:CAS:528:DyaK2sXit12qsb0%3D Occurrence Handle9071481

    CAS  PubMed  Google Scholar 

  23. BL Langdahl M Carstens L Stenkjaer EF Eriksen (2003) ArticleTitlePolymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone 32 297–310 Occurrence Handle10.1016/S8756-3282(02)00971-7 Occurrence Handle1:CAS:528:DC%2BD3sXit12gsLs%3D Occurrence Handle12667558

    Article  CAS  PubMed  Google Scholar 

  24. RW Keen H Snieder H Molloy et al. (2001) ArticleTitleEvidence of association and linkage disequilibrium between a noval polymorphism in the transforming growth factor β1 gene and hip bone mineral density: a study of female twins. Rheumatology 40 48–54 Occurrence Handle10.1093/rheumatology/40.1.48 Occurrence Handle1:CAS:528:DC%2BD3MXhtlKht7w%3D Occurrence Handle11157141

    Article  CAS  PubMed  Google Scholar 

  25. Y Yamada A Harada T Hosoi A Miyauchi K Ikeda H Ohta M Shiraki (2000) ArticleTitleAssociation of transforming growth factor β1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis. J Bone Miner Res 15 415–420 Occurrence Handle1:CAS:528:DC%2BD3cXitFaktr4%3D Occurrence Handle10750555

    CAS  PubMed  Google Scholar 

  26. F Bertoldo L D’Agruma F Furlan F Colapietro MT Lorenzi N Maioran A Iolascon L Zelante V LoCascio P Gasparini (2000) ArticleTitleTransforming growth factor-beta 1 gene polymorphism, bone turnover, and bone mass in Italian postmenopausal women. J Bone Miner Res 15 634–639 Occurrence Handle1:CAS:528:DC%2BD3cXisFWmtr0%3D Occurrence Handle10780855

    CAS  PubMed  Google Scholar 

  27. EA Thompson S Deeb D Walker AG Motulsky (1988) ArticleTitleThe direction of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. Am J Hum Genet 42 113–124 Occurrence Handle1:STN:280:BieC3czlsVY%3D Occurrence Handle2892394

    CAS  PubMed  Google Scholar 

  28. A Kung (1996) The prevalence and risk factors of fractures in Hong Kong. SK Lam (Eds) The Health of the elderly in Hong Kong. Hong Kong University Press Hong Kong 161–172

    Google Scholar 

  29. V Hinke T Seck C Clanget C Scheidt-Nave R Ziegler J Pfeilschifter (2001) ArticleTitleAssociation of transforming growth factor-beta1 (TGF beta1) T29 →C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF beta1 in a population-based sample of postmenopausal German women. Calcif Tissue Int 69 315–320

    Google Scholar 

  30. E Ziv J Cauley P Morin R Saiz W Browner (2003) ArticleTitleNo association between the TGF-β1 Leu10Pro polymorphism and osteoporosis among white women in United Sates. Am J Med 114 227–231

    Google Scholar 

  31. Y Yamada F Ando N Nilno H Shimokata (2003) ArticleTitleAssociation of polymorphisms of interleukin-6, osteocalcin, and vitamin D receptor genes, alone or in combination, with bone mineral density in community-dwelling Japanese women and men. J Clin Endocrinol Metab 88 3372–3378 Occurrence Handle10.1210/jc.2002-021449 Occurrence Handle1:CAS:528:DC%2BD3sXlslaiur0%3D Occurrence Handle12843190

    Article  CAS  PubMed  Google Scholar 

  32. P Garnero E Sornay-Rendu F Doboeuf PD Delmas (1999) ArticleTitleMarkers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res 14 1614–1621 Occurrence Handle1:STN:280:DyaK1Mzpslyksg%3D%3D Occurrence Handle10469291

    CAS  PubMed  Google Scholar 

  33. CJ Rosen CH Chesnurt SuffixIII NJS Mallinak (1997) ArticleTitleThe predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement with calcium supplementation. J Clin Endocrinol Metab 82 1904–1910 Occurrence Handle1:CAS:528:DyaK2sXjs1ent7Y%3D Occurrence Handle9177404

    CAS  PubMed  Google Scholar 

  34. BJ Riis MA Hansen AM Jensen K Overgaard C Christiansen (1996) ArticleTitleLow bone mass and fast rate of bone loss at menopause: equal risk factors for facture: A 15-year follow-up study. Bone 19 9–12 Occurrence Handle1:STN:280:BymH38jms1E%3D Occurrence Handle8830981

    CAS  PubMed  Google Scholar 

  35. R Eastell I Barton RA Hannon A Chines P Garnero PD Delmas (2003) ArticleTitleRelationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18 1051–1056 Occurrence Handle1:CAS:528:DC%2BD3sXkslOhsb0%3D Occurrence Handle12817758

    CAS  PubMed  Google Scholar 

  36. HG Stunnenberg (1993) ArticleTitleMechanisms of transactivation by retinoic acid receptors. Bioassays 15 309–315 Occurrence Handle1:CAS:528:DyaK3sXmtFOnuro%3D

    CAS  Google Scholar 

  37. DJ Grainger CM Witchell JC Metcalfe (1995) ArticleTitleTamoxifen elevates transforming growth factor-beta and suppresses diet-induced formation of lipid lesions in mouse aorta. Nat Med 1 1067–1073 Occurrence Handle1:CAS:528:DyaK2MXosVGnsr4%3D Occurrence Handle7489365

    CAS  PubMed  Google Scholar 

  38. DJ Grainger K Heathcote MN Chiano (1999) ArticleTitleGenetic control of the circulating concentration of transforming growth factor type β. Hum Mol Genet 1 93–97 Occurrence Handle10.1093/hmg/8.1.93

    Article  Google Scholar 

Download references

Acknowledgments

We thank K. S. Lau for technical assistance, the staff of Osteoporosis Centre, Queen Mary Hospital for assisting in the project and Mr. Stanley Yeung for statistical advice. The study was supported by the CRCG Grant, the University Department of Medicine Research Grant and the Endocrine and Osteoporosis Research Fund, University of Hong Kong.

Author information

Authors and Affiliations

  1. Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC

    H. H. L. Lau, A. Y. Y. Ho & A. W. C. Kung

  2. Department of Orthopaedic Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC

    K. D. K. Luk

Authors
  1. H. H. L. Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Y. Y. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. D. K. Luk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. W. C. Kung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. W. C. Kung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lau, H.H.L., Ho, A.Y.Y., Luk, K.D.K. et al. Transforming Growth Factor-β1 Gene Polymorphisms and Bone Turnover, Bone Mineral Density and Fracture Risk in Southern Chinese Women. Calcif Tissue Int 74, 516–521 (2004). https://doi.org/10.1007/s00223-004-0163-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-004-0163-4

Keywords

Search

Navigation