Skip to main content
SpringerLink
Log in

Sp1 polymorphism in collagen I α1 gene is associated with osteoporosis in lumbar spine of Mexican women

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The Sp1 binding site polymorphism in collagen type I alpha 1 gene (COLIA1) has been associated with osteoporosis (OP) and bone mineral density (BMD). The aim of this study was to explore the association of this polymorphism with OP and BMD in the Mexican population by polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) procedure. Allelic and genotypic frequencies from the Sp1 polymorphism were determined in 100 women with OP, 100 women without OP and 500 subjects from general Mexican population (GMP). Distribution of Sp1 polymorphism was in Hardy–Weinberg equilibrium. In spite of population structure due to racial mix in Mexican population, associations with OP were demonstrated. The frequency of “s” allele was significantly higher in women with OP (35%) than in women without OP (11%; P < 0.00001). Interestingly, “ss” genotype, was exclusive of women with OP and was associated with low BMD (0.588 ± 0.077 g/cm2) in contrast to “SS” genotype (0.733 ± 0.039 g/cm2; P = 0.0001). This work confirms the association of Sp1 polymorphism with low BMD and OP in Mexican population and make sure to use Sp1 as a genetic marker for OP in our population.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement 2000 17(1):1–45

  2. Stewart TL, Ralston SH (2000) Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol 166(2):235–245

    Article  PubMed  CAS  Google Scholar 

  3. Guthrie JR, Dennerstein L, Wark JD (2000) Risk factors for osteoporosis: a review. Medscape Womens Health 5(4):E1

    PubMed  CAS  Google Scholar 

  4. Eisman JA (1999) Genetics of osteoporosis. Endocr Rev 20(6):788–804

    Article  PubMed  CAS  Google Scholar 

  5. Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH (1996) Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 14(2):203–205

    Article  PubMed  CAS  Google Scholar 

  6. Mann V, Hobson EE, Li Baohua et al (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Investig 107(7):899–907

    Article  PubMed  CAS  Google Scholar 

  7. Bernard M, Martínez ME, Escalona M et al (2002) Polymorphism in the type I collagen (COLIA1) gene and risk of fractures in postmenopausal women. Bone 30(1):223–228

    Article  Google Scholar 

  8. Navarro MC, Sosa M, del Pino-Montes J et al (2007) Collagen type 1 (COL1A1) Sp1 binding site polymorphism is associated with osteoporotic fractures but not with bone density in post-menopausal women from the Canary island: a preliminary study. Aging Clin Exp Res 19(1):4–9

    PubMed  CAS  Google Scholar 

  9. Weichetová M, Stepán JJ, Michalská D, Haas T, Pols HAP, Uitterlinden AG (2000) COLIAI polymorphism contributes to bone mineral density to assess prevalent wrist fractures. Bone 26(3):287–290

    Article  PubMed  Google Scholar 

  10. McGuigan FE, Reid DM, Ralston SH (2000) Suceptibility to osteoporotic fracture is determined by allelic variation at the Sp1 site, rather than other polymorphic sites at the COLIAI locus. Osteoporos Int 11(4):338–343

    Article  PubMed  CAS  Google Scholar 

  11. Langdahl BL, Ralston SH, Grant SF, Eriksen EF (1998) An Sp1 binding site polymorphism in the COL1A1 gene predicts osteoporotic fractures in men and women. J Bone Miner Res 13(9):1384–1389

    Article  PubMed  CAS  Google Scholar 

  12. Nguyen TV, Esteban LM, White CP et al (2005) Contribution of the collagen I alpha1 and vitamin D receptor genes to the risk of hip fracture in elderly women. J Clin Endocrinol Metab 90(12):6575–6579

    Article  PubMed  CAS  Google Scholar 

  13. Utterlinden AG, Weel AE, Burger H et al (2001) Interaction between the vitamin D receptor gene and collagen type I α1 gene in susceptibility for fracture. J Bone Miner Res 16(2):379–385

    Article  Google Scholar 

  14. Grant SFA, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH (1996) Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type 1 α I gene. Nat Genet 14(2):203–205

    Article  PubMed  CAS  Google Scholar 

  15. Macdonald HM, Mcguigan FA, New SA, Campbell MK (2001) COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss. J Bone Miner Res 16(9):1634–1641

    Article  PubMed  CAS  Google Scholar 

  16. Efstathiadou Z, Kranas V, Ioannidis JP, Georgiou I, Tsatsaoulis A (2001) The Sp1 polymorphism and not vitamin D receptor or estrogen receptor gene polymorphisms, determines bone mineral density in postmenopausal Greek women. Osteoporos Int 12(4):326–331

    Article  PubMed  CAS  Google Scholar 

  17. Roux C, Dougados M, Abel L, Mercier G, Leucotte G (1998) Association of a polymorphism in the collagen 1 α1 gene with osteoporosis in French women. Arthritis Rheum 41(1):187–188

    Article  PubMed  CAS  Google Scholar 

  18. Braga V, Mottes M, Mirandola S et al (2000) Association of CTR and COLIA1 alleles with BMD values in peri-and postmenopausal women. Calcif Tissue Int 67(5):361–366

    Article  PubMed  CAS  Google Scholar 

  19. Alvarez L, Oriola J, Jo J et al (1999) Collagen type I alpha 1 gene Sp1 polymorphism in premenopausal women with primary osteoporosis: improved detection of Sp1 binding site polymorphism in the collagen type 1 gene. Clin Chem 45(6 Pt 1):904–906

    PubMed  CAS  Google Scholar 

  20. Uitterlinden AG, Burger H, Huang Q et al (1998) Relation of alleles of the collagen type 1 α1 gene to bone density and risk of osteoporotic fractures in postmenopausal women. N Engl J Med 338(15):1016–1021

    Article  PubMed  CAS  Google Scholar 

  21. Yazdanpanah N, Rivadeneira F, van Meurs JB et al (2007) The 1997 G/T and Sp1 polymorphisms in the collagen type I alpha1 (COLIA1) gene in relation to changes in femoral neck bone mineral density and the risk of fracture in the elderly: the Rotterdam study. Calcif Tissue Int 81(1):18–25

    Article  PubMed  CAS  Google Scholar 

  22. Keen RW, Woodford-Richens KL, Grant SFA, Ralston SH, Lanchbury JS, Spector TD (1999) Association of polymorphism at the type I collagen (COLIA1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover. Arthritis Rheum 42(2):285–290

    Article  PubMed  CAS  Google Scholar 

  23. Efstathiadou Z, Tsatsoulis A, Ioannidis JP (2001) Association of collagen I α1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J Bone Miner Res 16(9):1586–1592

    Article  PubMed  CAS  Google Scholar 

  24. Mann V, Ralston S (2003) Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 32(6):711–717

    Article  PubMed  CAS  Google Scholar 

  25. Ralston SH, Utterlinden AG, Brandi ML et al (2006) Large scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med 3(4):e90

    Article  PubMed  Google Scholar 

  26. Sambrook J, Fritsh EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  27. Köler K, Bickeböller H (2006) Case-control association test correcting for population stratification. Ann Hum Genet 70(Pt 1):98–115

    Article  Google Scholar 

  28. Callafel F, Shuster A, Speed WC, Kidd JR, Kidd KK (1998) Short tandem repeat polymorphism evolution in humans. Eur J Hum Genet 6(1):38–49

    Article  Google Scholar 

  29. Thomas DC, Witte JS (2002) Point: population stratification: a problem for case-control studies of candidate-gene associations? Cancer Epidemiol Biomark Prev 11(6):505–512

    Google Scholar 

  30. Hoggart CJ, Parra EJ, Shriver MD et al (2003) Control of confounding of genetic associations in stratified populations. Am J Hum Genet 72(6):1492–1504

    Article  PubMed  CAS  Google Scholar 

  31. Gómez R, Magaña JJ, Cisneros B et al (2007) Association of the estrogen receptor alfa gene polymorphism with osteoporosis in the Mexican population. Clin Genet 72(6):574–581

    Article  PubMed  Google Scholar 

  32. Peris P, Alvarez L, Oriola J, Guañabens N, Monegal A (2000) Collagen type I alpha I gene polymorphism in idiopathic osteoporosis in men. Rheumatology (Oxf) 39(11):1222–1225

    Article  CAS  Google Scholar 

  33. Suuriniemi M, Kovanen V, Mahonen A et al (2006) Col 1A1 Sp1 polymorphism associates with bone density in early puberty. Bone 39(3):591–597

    Article  PubMed  CAS  Google Scholar 

  34. Bustamante M, Nogues X, Enjuanes A et al (2007) Col 1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporos Int 18(2):235–243

    Article  PubMed  CAS  Google Scholar 

  35. Cavalli-Sforza LL, Cavalli-Sforza F (1995) The great human diasporas. Addison-Wesley, New York

    Google Scholar 

  36. Lidén M, Wilén B, Ljunghall S, Melhus H (1998) Polymorphism at Sp 1 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(4):293–295

    Article  PubMed  Google Scholar 

  37. Aerseens J, Dequeker J, Peeters J, Breeman S, Broos P, Boonen S (2000) Polymorphisms of the VDR, ER and COL IA1 genes and osteoporotic hip fracture in elderly postmenopausal women. Osteoporos Int 11(7):583–591

    Article  Google Scholar 

  38. Ashford RU, Lchetti M, McCloskey EV et al (2001) Studies of bone density, quantitative ultrasound, and vertebral fractures in relation to collagen type I alpha 1 alleles in elderly women. Calcif Tissue Int 68(6):348–351

    Article  PubMed  CAS  Google Scholar 

  39. Hubacek JA, Weichetová M, Bohuslavova R, Skodova Z, Stepán JJ, Adamkova V (2006) No associations between genetic polymorphisms of TGF-beta, PAI-1, and Col1A1, and bone mineral density in Caucasian females. Endocr Regul 40(4):107–112

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Council of Science and Technology (CONACYT) Project: Salud 2-2003-CO1-30.

Author information

Authors and Affiliations

  1. Department of Genetics, National Rehabilitation Institute, Calzada Mexico-Xochimilco No. 289, Arenal de Guadalupe, Tlalpan, CP 14389, Mexico City, Mexico

    Edith Falcón-Ramírez, Leonora Casas-Avila, Antonio Miranda, Rocío Gómez & Margarita Valdés-Flores

  2. Orthopedia Service, National Rehabilitation Institute, Mexico City, Mexico

    Pilar Diez

  3. Department of Genomic Medicine and Environmental Toxicology, Biomedical Investigation Institute, UNAM, Mexico City, Mexico

    Clementina Castro & Julieta Rubio

Authors
  1. Edith Falcón-Ramírez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leonora Casas-Avila
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pilar Diez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clementina Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Julieta Rubio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rocío Gómez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Margarita Valdés-Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Margarita Valdés-Flores.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Falcón-Ramírez, E., Casas-Avila, L., Miranda, A. et al. Sp1 polymorphism in collagen I α1 gene is associated with osteoporosis in lumbar spine of Mexican women. Mol Biol Rep 38, 2987–2992 (2011). https://doi.org/10.1007/s11033-010-9963-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-9963-y

Keywords

Search

Navigation