Skip to main content
SpringerLink
Log in

The c.29T>C polymorphism of the transforming growth factor beta-1 (TGFB1) gene, bone mineral density and the occurrence of low-energy fractures in patients with inflammatory bowel disease

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Gastrointestinal tract conditions are frequently associated with low bone mineral density and increased risk of fractures due to osteoporosis, the latter concerning particularly inflammatory bowel disease (IBD) patients. One of the candidate genes involved in osteoporosis is the transforming growth factor beta-1 (TGFB1) whose polymorphisms may be responsible for the development of this disease. The aim of this study was to analyse the frequency of TGFB1 polymorphic variants and determine the association between the c.29T>C TGFB1 polymorphism, and bone mineral density and fractures in IBD patients. The study subjects included 198 IBD patients [100 suffering from Crohn’s disease (CD) and 98 from ulcerative colitis (UC)] and 41 healthy volunteers as a control group. Densitometric bone measurements were obtained using dual energy X-ray absorptiometry. The TGFB1 genotyping was conducted using restriction fragments length polymorphism. We conducted an analysis of genotype distribution’s concordance with Hardy–Weinberg equilibrium. We found statistically significant differences in lumbar spine (L2–L4) and femoral neck BMD and T-scores between CD, UC and control subgroups. The distribution of TGFB1 polymorphic variants among CD and UC patients was concordant with Hardy–Weinberg equilibrium. There were no statistically significant differences in densitometric parameters (lumbar spine and femoral neck BMD, T-score, and Z-score) between carriers of different TGFB1 polymorphisms among IBD (CD and UC) patients nor among controls. We have found no statistically significant differences in the prevalence of low-energy fractures between groups of different TGFB1 polymorphic variant carriers. The allele dose effect, recessive effect and dominant effect analysis did not show an association between low-energy fractures and the TGFB1 polymorphisms among CD and UC patients. We have not observed an association between the c.29T>C TGFB1 polymorphic variant and the bone mineral density within the cancellous and cortical bones (L2–L4 and femoral neck, respectively), or the occurrence of fractures among the IBD patients and their family members.

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

Fig. 1

Similar content being viewed by others

References

  1. Sawczenko A, Sandahu BK, Logan RF, Jenkins H, Taylor CJ, Mian S, Lynn R (2001) Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet 357(9262):1093–1094

    Article  CAS  PubMed  Google Scholar 

  2. Scholmerich J (2000) Inflammatory bowel disease at the end of its first century. Hepatol Gastroenterol 47:2–4

    CAS  Google Scholar 

  3. Rider CC (2006) Heparin/heparan sulphate binding in the TGF-b cytokine superfamily. biochem. Soc Trans 34:458–460

    CAS  Google Scholar 

  4. Mundy GR (1991) The effects of TGF-beta on bone. Ciba Found Symp 157:137–143

    CAS  PubMed  Google Scholar 

  5. Uitterlinden AG, Burger H, Huang Q, Yue F, McGuigan FE, Grant SF, Hofman A, van Leeuwen JP, Pols HA, Ralston SH (1998) Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med 338:1016–1021

    Article  CAS  PubMed  Google Scholar 

  6. Whyte MP, Totty WG, Novack DV, Zhang X, Wenkert D, Mumm S (2011) Camurati-Engelmann disease: unique variant featuring a novel mutation in TGFβ1 encoding transforming growth factor β 1 and a missense change in TNFSF11 encoding RANK ligand. J Bone Miner Res 26(5):920–933

    Article  CAS  PubMed  Google Scholar 

  7. Davidson ENB, Vitters EL, van der Kraan PM, van den Berg WB (2006) Expression of transforming growth factor-beta (TGFbeta) and the TGFbeta signalling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation. Ann Rheum Dis 15:1414–1421

    Article  Google Scholar 

  8. McGuigan FE, Macdonald HM, Bassiti A, Farmer R, Bear S, Stewart A, Black A, Fraser WD, Welsh F, Reid DM (2007) Large-scale population-based study shows no association between common polymorphisms of the TGFB1 gene and BMD in women. J Bone Miner Res 22:195–202

    Article  CAS  PubMed  Google Scholar 

  9. Muthuri SG, Doherty S, Zhang W, Maciewicz RA, Muir KR, Doherty M (2013) Gene-environment interaction between body mass index and transforminggrowthfactor beta 1 (TGFβ1) gene in knee and hip osteoarthritis. Arthritis Res Ther 15(2):R52. doi:10.1186/ar4214

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rodríguez-Bores L, Barahona-Garrido J, Yamamoto-Furusho JK (2007) Basic and clinical aspects of osteoporosis in inflammatory bowel disease. World J Gastroenterol 13(46):6156–6165

  11. Alayli G, Kara N, Tander B, Canturk F, Gunes S, Bagci H (2009) Association of transforming growth factorb1 gene polymorphism with rheumatoid arthritis in a Turkish population. Joint Bone Spine 76:20–23

    Article  CAS  PubMed  Google Scholar 

  12. Healy J, Dionne J, Belanger H, Larivie`re M, Beaulieu P, Labuda D, Sinnett D (2009) Functional impact of sequence variation in the promoter region of TGFB1. Int J Cancer 125:1483–1489

    Article  CAS  PubMed  Google Scholar 

  13. Park BL, Han IK, Lee HS, Kim LH, Kim SJ, Shin HD (2003) Identification of novel variants in transforming growth factor-beta 1 (TGFB1) gene and association analysis with bone mineral density. Hum Mutat 22(3):257–258

    Article  Google Scholar 

  14. Crane JL, Cao X (2014) Bone marrow mesenchymal stem cells and TGF-β signaling in bone remodeling. J Clin Invest 124(2):466–472

  15. Janssens K et al (2000) Mutations in the gene encoding the latency-associated peptide of TGF-β 1 cause Camurati-Engelmann disease. Nat Genet 26(3):273–275

    Article  CAS  PubMed  Google Scholar 

  16. Janssens K, ten DP, Ralston, Bergmann SH, Van C (2003) HW. Transforming growth factor-β 1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein. J Biol Chem 278(9):7718–7724

    Article  CAS  PubMed  Google Scholar 

  17. Kinoshita A et al (2000) Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat Genet 26(1):19–20

    Article  CAS  PubMed  Google Scholar 

  18. Saito T, Kinoshita A, Yoshiura K, Makita Y, Wakui K, Honke K, Niikawa N, Taniguchi N (2001) Domain-specific mutations of a transforming growth factor (TGF)-β 1 latency-associated peptide cause Camurati-Engelmann disease because of the formation of a constitutively active form of TGF-β1. J Biol Chem 276(15):11469–11472

    Article  CAS  PubMed  Google Scholar 

  19. Bustamante M, Nogués X, Enjuanes A, Elosua R, García-Giralt N, Pérez-Edo L, Cáceres E, Carreras R, Mellibovsky L, Balcells S, Díez-Pérez A, Grinberg D (2007) COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporos Int 18:235–243

    Article  CAS  PubMed  Google Scholar 

  20. Bierie B, Moses HL (2006) TGF b: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 6:506–520

    Article  CAS  PubMed  Google Scholar 

  21. Itonaga I, Sabokbar A, Sun SG, Kudo O, Danks L, Ferguson D, Fujikawa Y, Athanasou NA (2004) Transforming growth factor-beta induces osteoclast formation in the absence of RANKL. Bone 34:57.64

    Article  PubMed  Google Scholar 

  22. Kalak R, Drwęska N, Słomski R, Wawrzyniak A, Marcinkowska M, Celczyńska-Bajew L, Horst-Sikorska W (2008) Association analysis in the search for genes responsible for polygenic diseases. The theory and practice of DNA analysis. Edited by Ryszard Słomski. The Publishing House of the Poznan University of Life Sciences, pp 444–452 (in Polish)

  23. Yamada Y, Miyauchi A, Goto J, Takagi Y, Okuizumi H, Kanematsu M, Hase M, Takai H, Harada A, Ikeda K (1998) Association of a polymorphism of the transforming growth factor-b1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res 13(10):1569–1576

    Article  CAS  PubMed  Google Scholar 

  24. Ziv E, Kahn A, Cauley J, Morin P, Saiz R, Browner W (2003) No association between the TGF-beta 1 Leu10Pro polymorphism and osteoporosis among white women in the United States. Am J Med 114(3):227–231

    Article  CAS  PubMed  Google Scholar 

  25. Langdahl BL, Carstens M, Stenkjær L, Eriksen EF (2003) Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone 32:297–310

    Article  CAS  PubMed  Google Scholar 

  26. Langdahl BL, Uitterlinden AG, Ralston SH, Trikalinos TA, Balcells S, Brandi ML, Scollen S, Lips P, Lorenc R, Obermayer-Pietsch B, Reid DM, Bruges Armas J, Arp PP, Bassiti A, Bustamante M, Husted LB, Carey AH, Pérez Cano R, Dobnig H, Dunning AM, Fahrleitner-Pammer A, Falchetti A, Karczmarewicz E, Kruk M, van Leeuwen JPTM, Masi L, van Meurs J.B.J., Mangion J, McGuigan F.E.A., Mellibovsky L, Mosekilde L, Nogués X, Pols H.A.P., Reeve J, Renner W, Rivadeneira F, van Schoor NM, Ioannidis J.P.A. (2008) Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study. Bone 42:969–981

    Article  CAS  PubMed  Google Scholar 

  27. Drwęska-Matelska N (2013) Polymorphisms in bone tissue metabolism genes and susceptibility to osteoporosis. PhD thesis in Polish, Department of Biochemistry and Biotechnology, Poznan University of Life Sciences; supervisor: Prof. Ryszard Słomski, auxiliary supervisor: Dr Marlena Szalata, Poland

  28. Hinke V, Seck T, Clanget C, Scheidt-Nave C, Ziegler R, Pfeilschifter J (2001) Association of transforming growth factor-B1 (TGFB1) T29→C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF-B1 in a population-based sample of postmenopausal German women. Calcif Tissue Int 69:315–320

    Article  CAS  PubMed  Google Scholar 

  29. Dick IM, Devine A, Li S, Dhaliwal SS, Prince RL (2003) The T869C TGFB polymorphism is associated with fracture, bone mineral density, and calcaneal quantitative ultrasound in elderly women. Bone 33:335–341

    Article  CAS  PubMed  Google Scholar 

  30. Lau HH, Ho AY, Luk KD, Kung AW (2004) Transforming growth factor-beta1 gene polymorphisms and bone turnover, bone mineral density and fracture risk in southern Chinese women. Calcif Tissue Int 74(6):516–521

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

In memory of the late Professor Wanda Horst-Sikorska, who supported us her knowledge, ideas and kindness.

Funding

This study was financed from the project of Polish Ministry of Science and Higher Education nr 402481737.

Author information

Author notes

  1. Linke—deceased.

Authors and Affiliations

  1. Department of Gastroenterology, Human Nutrition and Internal Diseases, University of Medical Sciences, Przybyszewskiego Street 49, 60-355, Poznan, Poland

    I. Krela-Kaźmierczak, A. Szymczak, P. Eder, L. Łykowska-Szuber & K. Linke

  2. Department of Computer Science and Statistics, University of Medical Sciences, Poznan, Poland

    M. Michalak

  3. Department of Family Medicine, University of Medical Sciences, Poznan, Poland

    A. Wawrzyniak

  4. Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland

    M. Kaczmarek-Ryś, M. Skrzypczak-Zielińska & R. Słomski

  5. Institute of Natural Fibres and Medicinal Plants, Poznan, Poland

    N. Drwęska-Matelska

Authors
  1. I. Krela-Kaźmierczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Michalak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Wawrzyniak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Szymczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Eder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Łykowska-Szuber
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Kaczmarek-Ryś
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N. Drwęska-Matelska
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. Skrzypczak-Zielińska
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K. Linke
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R. Słomski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Krela-Kaźmierczak.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest in the authorship or publication of contribution.

Ethical approval

The study subjects included inflammatory bowel disease (IBD) patients from the Clinic of Gastroenterology, Human Nutrition and Internal Diseases of the Poznan University of Medical Sciences (Poznan, Poland), and forty-one healthy volunteers without IBD All patients gave their written consent to participate in the genetic testing and the study was approved by the Bioethical Committee of the Poznan University of Medical Sciences (Poznan, Poland; Approval No. 92/09).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krela-Kaźmierczak, I., Michalak, M., Wawrzyniak, A. et al. The c.29T>C polymorphism of the transforming growth factor beta-1 (TGFB1) gene, bone mineral density and the occurrence of low-energy fractures in patients with inflammatory bowel disease. Mol Biol Rep 44, 455–461 (2017). https://doi.org/10.1007/s11033-017-4131-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-017-4131-2

Keywords

Search

Navigation