Skip to main content
SpringerLink
Log in

Association of the Collagen Type 1 (COL1A 1) Sp1 Binding Site Polymorphism to Femoral Neck Bone Mineral Density and Wrist Fracture in 1044 Elderly Swedish Women

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the “s” allele (P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the “s” allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1–6.8) for the ss homozygotes and 1.4 (95% CI 1.0–2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogenous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the “s” allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.

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. PH Byers RD Steiner (1992) ArticleTitleOsteogenesis imperfecta. Annu Rev Med 43 269–282

    Google Scholar 

  2. V Mann EE Hobson L Baohua TL Stewart SFA Grant SP Robins RM Aspden SH Ralston (2001) ArticleTitleA COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107 899–907 Occurrence Handle1:CAS:528:DC%2BD3MXisFWhtrY%3D Occurrence Handle11285309

    CAS  PubMed  Google Scholar 

  3. FE McGuigan DM Reid SH Ralston (2000) ArticleTitleSusceptibility to osteoporotic fracture is determined by allelic variation at the Sp1 site, rather than other polymorphic sites at the COL1A1 locus. Osteoporosis Int 11 338–343 Occurrence Handle10.1007/s001980070123 Occurrence Handle1:CAS:528:DC%2BD3cXmtVakt78%3D

    Article  CAS  Google Scholar 

  4. SF Grant DM Reid G Blake R Herd I Fogelman SH Ralson (1996) ArticleTitleReduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 14 IssueID2 203–205 Occurrence Handle1:CAS:528:DyaK28XmtVKntb4%3D Occurrence Handle8841196

    CAS  PubMed  Google Scholar 

  5. PJ Bornstein . McKay JK Morishima S Devarayalu RE Gelinas (1987) ArticleTitleRegulatory elements in the first intron contribute to transcriptional control of the human alpha 1(I) collagen gene. Proc Natl Acad Sci USA 84 IssueID24 8869–8873 Occurrence Handle1:CAS:528:DyaL1cXhtVOgsLw%3D Occurrence Handle3480516

    CAS  PubMed  Google Scholar 

  6. P Garnero O Borel SF Grant SH Ralston PD Delmas (1998) ArticleTitleCollagen I alfa 1 Sp1 polymorphism, bone mass, and bone turnover in healthy French premenopausal women: the OFELY study. J Bone Miner Res 13 813–817 Occurrence Handle1:CAS:528:DyaK1cXjsVaqurk%3D Occurrence Handle9610745

    CAS  PubMed  Google Scholar 

  7. AG Uitterlinden H Burger Q Huang F Yue FE McGuigan SF Grant A Hofman JP van Leeuwen HA Pols SH Ralson (1998) ArticleTitleRelation of alleles of the collagen type I alfa 1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med 338 1016–1021 Occurrence Handle1:STN:280:DyaK1c7otFOqug%3D%3D Occurrence Handle9535665

    CAS  PubMed  Google Scholar 

  8. RW Keen KL Woodford-Richens SF Grant SH Ralston JS Lanchbury T Spector (1999) ArticleTitleAssociation polymorphisms at the type I collagen (COL1A1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover. Arthritis Rheum 42 285–290 Occurrence Handle10.1002/1529-0131(199902)42:2<285::AID-ANR10>3.0.CO;2-3 Occurrence Handle1:CAS:528:DyaK1MXhtlars7Y%3D Occurrence Handle10025922

    Article  CAS  PubMed  Google Scholar 

  9. RU Ashford M Luchetti EV McClosky RL Gray KC Pande A Dey K Kayan SH Ralston JA Kanis (2001) ArticleTitleStudies on bone density, quantitative ultrasound, and vertebral fractures in relation to collagen type I alfa 1 alleles in elderly women. Calcif Tissue Int 68 348–351 Occurrence Handle1:CAS:528:DC%2BD3MXlslShs74%3D Occurrence Handle11685422

    CAS  PubMed  Google Scholar 

  10. A Heegaard HL Jorgensen AW Vestergaard C Hassager SH Ralston (2000) ArticleTitleLack of influence of collagen type Iα1 Sp1 binding site polymorphism on the rate of bone loss in a cohort of postmenopausal Danish women followed for 18 years. Calcif Tissue Int 66 409–413 Occurrence Handle10.1007/s002230010083 Occurrence Handle1:CAS:528:DC%2BD3cXksVSjsL0%3D Occurrence Handle10821875

    Article  CAS  PubMed  Google Scholar 

  11. FG Hustmyer G Liu CC Johnston J Christian M Peacock (1999) ArticleTitlePolymorphism at an Sp1 binding site of COL1A1 and bone mineral density in premenopausal female twins and elderly fracture patients. Osteoporos hit 9 346–350 Occurrence Handle10.1007/s001980050157 Occurrence Handle1:STN:280:DC%2BD3c%2FhvFynug%3D%3D

    Article  CAS  Google Scholar 

  12. M Karlsson O Johnell KJ Obrant (1995) ArticleTitleIs bone mineral density advantage maintained long-term in previous weight lifters? Calcif Tissue Int 57 325–328 Occurrence Handle8564793

    PubMed  Google Scholar 

  13. MK Karlsson KJ Obrant BE Nilsson O Johnell (2000) ArticleTitleChanges in bone mineral, lean body mass and fat content as measured by dual energy X-ray absorptiometry: a longitudinal study. Calcif Tissue Int 66 97–109 Occurrence Handle1:CAS:528:DC%2BD3cXpslKiug%3D%3D Occurrence Handle10652954

    CAS  PubMed  Google Scholar 

  14. MK Karlsson KJ Obrant BE Nilsson O Johnell (1998) ArticleTitleBone mineral density assessed by quantitative ultrasound and dual energy X-ray absorptiometry. Acta Orthop Scand 69 189–193 Occurrence Handle1:STN:280:DyaK1c3msFCqsA%3D%3D Occurrence Handle9602782

    CAS  PubMed  Google Scholar 

  15. BL Langdahl SH Ralston SFA Grant EF Eriksen (1998) ArticleTitleAn Sp1 binding site polymorphism in the COL1A1 gene predicts osteoporotic fractures in both men and women. J Bone Miner Res 13 1384–1389

    Google Scholar 

  16. HM MacDonald FA McGuigan SA New MK Campbell MHN Golden SH Ralston DM Reid (2001) ArticleTitleCOL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss. J Bone Miner Res 16 1634–1641

    Google Scholar 

  17. SS Harris MS Patel DE Cole B Dawson-Hughes (2000) ArticleTitleAssociations of the collagen type Iα1 Sp1 polymorphism with five-year rates of bone loss in older adults. Calcif Tissue Int 66 268–271 Occurrence Handle10.1007/s002230010054 Occurrence Handle1:CAS:528:DC%2BD3cXivVChurs%3D Occurrence Handle10742443

    Article  CAS  PubMed  Google Scholar 

  18. M Sowers M Willing T Burns S Deschenes B Hollis M Crutchfield M Jannausch (1999) ArticleTitleGenetic markers, bone mineral density, and serum osteocalcin levels. J Bone Miner Res 14 1411–1419 Occurrence Handle1:CAS:528:DyaK1MXltlyltrs%3D Occurrence Handle10457274

    CAS  PubMed  Google Scholar 

  19. AG Uitterlinden AEAM Weel H Burger Y Fang CM van Duijn A Hofman JPTM van Leeuwen HAP Pols (2001) ArticleTitleInteraction between the vitamin D receptor gene and collagen type Iα1 gene in susceptibility for fracture. J Bone Miner Res 16 379–385 Occurrence Handle1:CAS:528:DC%2BD3MXptlyjsA%3D%3D Occurrence Handle11204438

    CAS  PubMed  Google Scholar 

  20. MA Brown MA Haughton SFA Grant AS Gunnell NK Henderson JA Eisman (2001) ArticleTitleGenetic control of bone density and turnover: role of the collagen Iα1, estrogen receptor, and vitamin D receptor genes. J Bone Miner Res 16 758–764 Occurrence Handle1:CAS:528:DC%2BD3MXislCktrY%3D Occurrence Handle11316004

    CAS  PubMed  Google Scholar 

  21. M Liden B Wilen S Ljunghall H Melhus (1998) ArticleTitlePolymorphism at the Sp1 binding site in the collagen type I alpha 1 gene does not predict bone mineral density in postmenopausal women in Sweden. Calcif Tissue Int 63 IssueID4 293–295 Occurrence Handle10.1007/s002239900529 Occurrence Handle1:CAS:528:DyaK1cXmsVeht78%3D Occurrence Handle9744986

    Article  CAS  PubMed  Google Scholar 

  22. Z Efstathiadou A Tsatsoulis JPA Ioannidis (2001) ArticleTitleAssociation of collagen Iα1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J Bone Miner Res 16 1586–1592 Occurrence Handle1:CAS:528:DC%2BD3MXmvV2qs7c%3D Occurrence Handle11547828

    CAS  PubMed  Google Scholar 

  23. S Valimäki R Tahtela K Kainulainen K Laitinen E Loyttyniemi R Sulkava M Valimäki K Kontula (2001) ArticleTitleRelation of collagen type Iα1 (COLIA1) and vitamin D receptor genotypes to bone mass, turnover, and fractures in early postmenopausal women and to hip fractures in elderly people. Eur J Int Med 12 48–56

    Google Scholar 

  24. M Weichetova JJ Stepan D Michalska T Haas HA Pols AG Uitterlinden (2000) ArticleTitleCOLIA1 polymorphism contributes to bone mineral density to assess prevalent wrist fractures. Bone 26 287–290 Occurrence Handle10.1016/S8756-3282(99)00280-X Occurrence Handle1:CAS:528:DC%2BD3cXhtFalsrc%3D Occurrence Handle10710003

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Alfred Österlund and Greta and Johan Kock Foundations and the Malmö University Hospital Funds.

Author information

Authors and Affiliations

  1. Department of Orthopedics, Lund University, Malmö University Hospital, Malmö, Sweden

    P. Gerdhem, K. Obrant & K. Åkesson

  2. Department of Medical Sciences, Uppsala , Sweden

    H. Brändström, F. Stiger, H. Melhus, Ö. Ljunggren & A. Kindmark

Authors
  1. P. Gerdhem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Brändström
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Stiger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Obrant
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Melhus
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ö. Ljunggren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Kindmark
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K. Åkesson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Åkesson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerdhem, P., Brändström, H., Stiger, F. et al. Association of the Collagen Type 1 (COL1A 1) Sp1 Binding Site Polymorphism to Femoral Neck Bone Mineral Density and Wrist Fracture in 1044 Elderly Swedish Women. Calcif Tissue Int 74, 264–269 (2004). https://doi.org/10.1007/s00223-002-2159-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-002-2159-2

Keywords

Search

Navigation