Skip to main content
SpringerLink
Log in

Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

A meta-analysis of studies was conducted involving 24,511 participants with 7,864 fractures in which polymorphisms in the 5′ flank of COL1A1 (rs1107946, rs2412298, and rs1800012) were related to osteoporosis phenotypes. Polymorphisms of all three sites were associated with BMD, and rs1800012 was associated with fracture but effect sizes were modest.

Introduction and hypothesis

Polymorphisms in the 5′ flank of COL1A1 gene have been implicated as genetic markers for susceptibility to osteoporosis, but previous studies have yielded conflicting results.

Methods

We conducted a meta-analysis of 32 studies including 24,511 participants and 7,864 fractures in which alleles at the -1997G/T (rs1107946), -1663in/delT (rs2412298), and Sp1 binding site polymorphisms (rs1800012) of COL1A1 had been related to bone mineral density (BMD) or fracture.

Results

For the Sp1 polymorphism, BMD values in TT homozygotes were 0.13 units [95% CI, 0.03 to 0.24] lower at the spine (p = 0.01) and 0.16 units [0.10 to 0.23] lower at the hip (\( p = {1} \times {1}{0^{ - {6}}} \)) than GG homozygotes. Clinical fractures were 1.31-fold [1.04–1.65] increased in TT homozygotes (p = 0.02) and vertebral fractures were 1.34-fold [1.01–1.77] increased (p = 0.04). We also observed associations between spine BMD and allelic variants at the -1997G/T (p = 0.05) and the -1663indelT (p = 0.009) sites. We found no association between alleles at the -1997G/T or -1663indelT sites and fracture but power was limited.

Conclusions

The COL1A1 Sp1 polymorphism is associated with a modest reduction in BMD and an increased risk of fracture, although we cannot fully exclude the possibility that the results may have been influenced by publication bias. Further studies are required to fully evaluate the contribution of the -1997G/T and -1663in/delT sites to these phenotypes and to determine if they interact with the Sp1 polymorphism to regulate susceptibility to osteoporosis.

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. Arden NK, Spector TD (1997) Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J Bone Miner Res 12:2076–2081

    Article  CAS  PubMed  Google Scholar 

  2. Knapp KM, Andrew T, MacGregor AJ, Blake GM, Fogelman I, Spector TD (2003) An investigation of unique and shared gene effects on speed of sound and bone density using axial transmission quantitative ultrasound and DXA in twins. J Bone Miner Res 18:1525–1530

    Article  PubMed  Google Scholar 

  3. Michaelsson K, Melhus H, Ferm H, Ahlbom A, Pedersen NL (2005) Genetic liability to fractures in the elderly. Arch Intern Med 165:1825–1830

    Article  PubMed  Google Scholar 

  4. Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Richards JB, Zillikens MC, Kavvoura FK, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Grundberg E, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra B, Pastinen T, Pols HA, Sigurdsson G, Soranzo N, Thorleifsson G, Thorsteinsdottir U, Williams FM, Wilson SG, Zhou Y, Ralston SH, van Duijn CM, Spector T, Kiel DP, Stefansson K, Ioannidis JP, Uitterlinden AG (2009) Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet 41:1119–1206

    Article  Google Scholar 

  5. Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD (2008) Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371:1505–1512

    Article  CAS  PubMed  Google Scholar 

  6. Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Snorradottir S, Center JR, Nguyen TV, Alexandersen P, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2009) New sequence variants associated with bone mineral density. Nat Genet 41:15–17

    Article  CAS  PubMed  Google Scholar 

  7. Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Center JR, Nguyen TV, Bagger Y, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2008) Multiple genetic loci for bone mineral density and fractures. N Engl J Med 358:2355–2365

    Article  CAS  PubMed  Google Scholar 

  8. Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107:899–907

    Article  CAS  PubMed  Google Scholar 

  9. Fang Y, van Meurs JB (2005) d'Alesio A, Jhamai M, Zhao H, Rivadeneira F, Hofman A, van Leeuwen JP, Jehan F, Pols HA, Uitterlinden AG. Promoter and 3′-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am J Hum Genet 77:807–823

    Article  CAS  PubMed  Google Scholar 

  10. Uitterlinden AG, Burger H, Huang Q, Yue F, McGuigan FEA, Grant SFA, Hofman A, van Leeuwen JPTM, Pols HAP, Ralston SH (1998) Relation of alleles of the collagen type I α 1 gene to bone density and risk of osteoporotic fractures in postmenopausal women. N Engl J Med 338:1016–1022

    Article  CAS  PubMed  Google Scholar 

  11. van Meurs JB, Trikalinos TA, Ralston SH, Balcells S, Brandi ML, Brixen K, Kiel DP, Langdahl BL, Lips P, Ljunggren O, Lorenc R, Obermayer-Pietsch B, Ohlsson C, Pettersson U, Reid DM, Rousseau F, Scollen S, Van HW, Agueda L, Akesson K, Benevolenskaya LI, Ferrari SL, Hallmans G, Hofman A, Husted LB, Kruk M, Kaptoge S, Karasik D, Karlsson MK, Lorentzon M, Masi L, McGuigan FE, Mellstrom D, Mosekilde L, Nogues X, Pols HA, Reeve J, Renner W, Rivadeneira F, van Schoor NM, Weber K, Ioannidis JP, Uitterlinden AG (2008) Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA 299:1277–1290

    Article  PubMed  Google Scholar 

  12. Langdahl BL, Uitterlinden AG, Ralston SH, Trikalinos TA, Balcells S, Brandi ML, Scollen S, Lips P, Lorenc R, Obermayer-Pietsch B, Reid DM, Armas JB, Arp PP, Bassiti A, Bustamante M, Husted LB, Carey AH, Perez CR, Dobnig H, Dunning AM, Fahrleitner-Pammer A, Falchetti A, Karczmarewicz E, Kruk M, van Leeuwen JP, Masi L, van Meurs JB, Mangion J, McGuigan FE, Mellibovsky L, Mosekilde L, Nogues X, Pols HA, Reeve J, Renner W, Rivadeneira F, van Schoor NM, Ioannidis JP (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 

  13. Richards JB, Kavvoura FK, Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Zillikens MC, Wilson SG, Mullin BH, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra BA, Pols HA, Sigurdsson G, Thorsteinsdottir U, Soranzo N, Williams FM, Zhou Y, Ralston SH, Thorleifsson G, van Duijn CM, Kiel DP, Stefansson K, Uitterlinden AG, Ioannidis JP, Spector TD (2009) Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med 151:528–537

    PubMed  Google Scholar 

  14. Ioannidis JP (2005) Why most published research findings are false. PLoS Med 2:e124

    Article  PubMed  Google Scholar 

  15. Kryukov GV, Shpunt A, Stamatoyannopoulos JA, Sunyaev SR (2009) Power of deep, all-exon resequencing for discovery of human trait genes. Proc Natl Acad Sci USA 106:3871–3876

    Article  CAS  PubMed  Google Scholar 

  16. Ralston SH, Uitterlinden AG, Brandi ML, Balcells S, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Scollen S, Bustamante M, Husted LB, Carey AH, Diez-Perez A, Dunning AM, Falchetti A, Karczmarewicz E, Kruk M, van Leeuwen JPTM, Meurs JB, Mangion J, McGuigan FE, Mellibovsky L, Monte FD, Pols HA, Reeve J, Reid DM, Renner W, Rivadeneira F, Schoor NM, Sherlock RE, Ioannidis JP (2006) Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med 3:e90

    Article  PubMed  Google Scholar 

  17. Trikalinos TA, Salanti G, Zintzaras E, Ioannidis JP (2008) Meta-analysis methods. Adv Genet 60:311–334

    Article  PubMed  Google Scholar 

  18. Uitterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Reeve J, Reid DM, Amidei A, Bassiti A, Bustamante M, Husted LB, ez-Perez A, Dobnig H, Dunning AM, Enjuanes A, Fahrleitner-Pammer A, Fang Y, Karczmarewicz E, Kruk M, van Leeuwen JP, Mavilia C, van Meurs JB, Mangion J, McGuigan FE, Pols HA, Renner W, Rivadeneira F, van Schoor NM, Scollen S, Sherlock RE, Ioannidis JP (2006) The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Intern Med 145:255–264

    CAS  PubMed  Google Scholar 

  19. Ioannidis JP, Ng MY, Sham PC, Zintzaras E, Lewis CM, Deng HW, Econs MJ, Karasik D, Devoto M, Kammerer CM, Spector T, Andrew T, Cupples LA, Duncan EL, Foroud T, Kiel DP, Koller D, Langdahl B, Mitchell BD, Peacock M, Recker R, Shen H, Sol-Church K, Spotila LD, Uitterlinden AG, Wilson SG, Kung AW, Ralston SH (2007) Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. J Bone Miner Res 22:173–183

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33:177–182

    Article  CAS  PubMed  Google Scholar 

  22. Efstathiadou Z, Tsatsoulis A, Ioannidis JP (2001) Association of collagen Ialpha 1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J Bone Miner Res 16:1586–1592

    Article  CAS  PubMed  Google Scholar 

  23. Garcia-Giralt N, Nogues X, Enjuanes A, Puig J, Mellibovsky L, Bay-Jensen A, Carreras R, Balcells S, Diez-Perez A, Grinberg D (2002) Two new single nucleotide polymorphisms in the COLIA1 upstream regulatory region and their relationship with bone mineral density. J Bone Miner Res 17:384–393

    Article  CAS  PubMed  Google Scholar 

  24. Stewart TL, Jin H, McGuigan FE, Albagha OM, Garcia-Giralt N, Bassiti A, Grinberg D, Balcells S, Reid DM, Ralston SH (2006) Haplotypes defined by promoter and intron 1 polymorphisms of the COLIA1 gene regulate bone mineral density in women. J Clin Endocrinol Metab 91:3575–3583

    Article  CAS  PubMed  Google Scholar 

  25. Yamada Y, Ando F, Niino N, Shimokata H (2005) Association of a -1997G– > T polymorphism of the collagen I alpha1 gene with bone mineral density in postmenopausal Japanese women. Hum Biol 77:27–36

    Article  PubMed  Google Scholar 

  26. Yazdanpanah N, Rivadeneira F, van Meurs JB, Zillikens MC, Arp P, Hofman A, van Duijn CM, Pols HA, Uitterlinden AG (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 81:18–25

    Article  CAS  PubMed  Google Scholar 

  27. Bustamante M, Nogues X, Enjuanes A, Elosua R, Garcia-Giralt N, Perez-Edo L, Caceres E, Carreras R, Mellibovsky L, Balcells S, ez-Perez 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 

  28. Gerdhem P, Brandstrom H, Stiger F, Obrant K, Melhus H, Ljunggren O, Kindmark A, Akesson K (2004) 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

    Article  CAS  PubMed  Google Scholar 

  29. Husted LB, Harslof T, Gonzalez-Bofill N, Schmitz A, Carstens M, Stenkjaer L, Langdahl BL (2009) Haplotypes of promoter and intron 1 polymorphisms in the COLIA1 gene are associated with increased risk of osteoporosis. Calcif Tissue Int 84:85–96

    Article  CAS  PubMed  Google Scholar 

  30. Nguyen TV, Esteban LM, White CP, Grant SF, Center JR, Gardiner EM, Eisman JA (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 90:6575–6579

    Article  CAS  PubMed  Google Scholar 

  31. Selezneva LI, Khusainova RI, Nurlygaianov RZ, Fazlyeva EA, Usenko KP, Lesniak OM, Khucnutdinova EK (2008) Association of polymorphisms and haplotypes in the 5′ region of COLIA1 gene with the risk of osteoporotic fractures in Russian women from Volga-Ural region. Genetika 44:219–225

    CAS  PubMed  Google Scholar 

  32. Weichetova M, Stepan JJ, Haas T, Michalska D (2005) The risk of Colles' fracture is associated with the collagen I alpha1 Sp1 polymorphism and ultrasound transmission velocity in the calcaneus only in heavier postmenopausal women. Calcif Tissue Int 76:98–106

    Article  CAS  PubMed  Google Scholar 

  33. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826

    CAS  PubMed  Google Scholar 

  34. Ioannidis JP, Patsopoulos NA, Evangelou E (2007) Uncertainty in heterogeneity estimates in meta-analyses. Br Med J 335:914–916

    Article  Google Scholar 

  35. Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test [see comments]. Br Med J 315:629–634

    CAS  Google Scholar 

  36. Harbord RM, Egger M, Sterne JA (2006) A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med 25:3443–3457

    Article  PubMed  Google Scholar 

  37. Ioannidis JP, Trikalinos TA (2007) An exploratory test for an excess of significant findings. Clin Trials 4:245–253

    Article  PubMed  Google Scholar 

  38. Braga V, Mottes M, Mirandola S, Lisi V, Malerba G, Sarton L, Bianchi G, Gatti D, Rossini M, Bianchini D, Adami S (2000) Association of CTR and COLIA1 alleles with BMD values in peri- and postmenopausal women. Calcif Tissue Int 67:361–366

    Article  CAS  PubMed  Google Scholar 

  39. Orwoll ES, Belknap JK, Klein RF (2001) Gender specificity in the genetic determinants of peak bone mass. J Bone Miner Res 16:1962–1971

    Article  CAS  PubMed  Google Scholar 

  40. Ralston SH, Galwey N, Mackay I, Albagha OM, Cardon L, Compston JE, Cooper C, Duncan E, Keen R, Langdahl B, McLellan A, O'Riordan J, Pols HA, Reid DM, Uitterlinden AG, Wass J, Bennett ST (2005) Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: the FAMOS study. Hum Mol Genet 14:943–951

    Article  CAS  PubMed  Google Scholar 

  41. Jin H, Van't Hof RJ, Albagha OM, Ralston SH (2009) Promoter and intron 1 polymorphisms of COL1A1 interact to regulate transcription and susceptibility to osteoporosis. Hum Mol Genet 18:2729–2738

    Article  CAS  PubMed  Google Scholar 

  42. Aerssens J, Dequeker J, Peeters J, Breemans S, Broos P, Boonen S (2000) Polymorphisms of the VDR, ER and COLIA1 genes and osteoporotic hip fracture in elderly postmenopausal women. Osteoporos Int 11:583–591

    Article  CAS  PubMed  Google Scholar 

  43. Valimaki S, Tahtela R, Kainulainen K, Laitinen K, Loyttyniemi E, Sulkava R, Valimaki M, Kontula K (2001) Relation of collagen type I alpha 1 (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 Intern Med 12:48–56

    Article  CAS  PubMed  Google Scholar 

  44. Jin H, Stewart TL, Hof RV, Reid DM, Aspden RM, Ralston S (2009) A rare haplotype in the upstream regulatory region of COL1A1 is associated with reduced bone quality and hip fracture. J Bone Miner Res 24:448–454

    Article  CAS  PubMed  Google Scholar 

  45. Ioannidis JP (2008) Effect of formal statistical significance on the credibility of observational associations. Am J Epidemiol 168:374–383

    Article  PubMed  Google Scholar 

  46. Wacholder S, Chanock S, Garcia-Closas M, El GL, Rothman N (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96:434–442

    Article  PubMed  Google Scholar 

  47. Alvarez-Hernandez D, Naves M, Diaz-Lopez JB, Gomez C, Santamaria I, Cannata-Andia JB (2003) Influence of polymorphisms in VDR and COLIA1 genes on the risk of osteoporotic fractures in aged men. Kidney Int 63:S14–S18

    Article  Google Scholar 

  48. Ashford RU, Luchetti M, McCloskey EV, Gray RL, Pande KC, Dey A, Kayan K, Ralston SH, Kanis JA (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 68:348–351

    Article  CAS  PubMed  Google Scholar 

  49. Bernad M, Martinez ME, Escalona M, Gonzalez ML, Gonzalez C, Garces MV, Del Campo MT, Martin ME, Madero R, Carreno L (2002) Polymorphism in the type I collagen (COLIA1) gene and risk of fractures in postmenopausal women. Bone 30:223–228

    Article  CAS  PubMed  Google Scholar 

  50. Braga V, Sangalli A, Malerba G, Mottes M, Mirandola S, Gatti D, Rossini M, Zamboni M, Adami S (2002) Relationship among VDR (BsmI and FokI), COLIA1, and CTR polymorphisms with bone mass, bone turnover markers, and sex hormones in men. Calcif Tissue Int 70:457–462

    Article  CAS  PubMed  Google Scholar 

  51. Efstathiadou Z, Kranas V, Ioannidis JP, Georgiou I, Tsatsoulis A (2001) The Sp1 COLIA1 gene polymorphism, and not vitamin D receptor or estrogen receptor gene polymorphisms, determines bone mineral density in postmenopausal Greek women. Osteoporos Int 12:326–331

    Article  CAS  PubMed  Google Scholar 

  52. Garnero P, Borel O, Grant SFA, Ralston SH, Delmas PD (1998) Collagen I α 1 polymorphism, bone mass and bone turnover in healthy French pre-menopausal women: the OFELY study. J Bone Miner Res 13:813–818

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  54. Harris SS, Patel MS, Cole DE, Dawson-Hughes B (2000) Associations of the collagen type I alpha 1 Sp1 polymorphism with five-year rates of bone loss in older adults. Calcif Tissue Int 66:268–271

    Article  CAS  PubMed  Google Scholar 

  55. Heegaard A, Jorgensen HL, Vestergaard AW, Hassager C, Ralston SH (2000) Lack of influence of collagen type I alpha 1 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

    Article  CAS  PubMed  Google Scholar 

  56. Hustmyer FG, Lui G, Johnston CC, Christian J, Peacock M (1999) Polymorphism at an Sp1 binding site of COLIA1 and bone mineral density in pre-menopausal female twins and elderly fracture patients. Osteoporos Int 9:346–350

    Article  CAS  PubMed  Google Scholar 

  57. Keen RW, Woodford-Richens KL, Grant SF, Ralston SH, Lanchbury JS, Spector TD (1999) Association of polymorphism at the type I collagen (COL1A1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover. Arthritis Rheum 42:285–290

    Article  CAS  PubMed  Google Scholar 

  58. Liden M, Wilen B, Ljunghall S, Melhus H (1998) Polymorphism at the 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 63:293–295

    Article  CAS  PubMed  Google Scholar 

  59. McGuigan FE, Reid DM, Ralston SH (2000) Susceptibility to osteoporotic fracture is determined by allelic variation at the Sp1 site, rather than other polymorphic sites at the COL1A1 locus. Osteoporos Int 11:338–343

    Article  CAS  PubMed  Google Scholar 

  60. McGuigan FEA, Armbrecht G, Smith R, Felsenberg D, Reid DM, Ralston SH (2001) Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping: a prospective, population-based study in men and women. Osteoporos Int 12:91–96

    Article  CAS  PubMed  Google Scholar 

  61. Mezquita-Raya P, Munoz-Torres M, de Dios LJ, Lopez-Rodriguez F, Quesada JM, Luque-Recio F, Escobar-Jimenez F (2002) Performance of COLIA1 polymorphism and bone turnover markers to identify postmenopausal women with prevalent vertebral fractures. Osteoporos Int 13:506–512

    Article  CAS  PubMed  Google Scholar 

  62. Peris P, Alvarez L, Oriola J, Guanabens N, Monegal A, De Osaba MJ, Jo J, Pons F, Ballesta AM, Munoz-Gomez J (2000) Collagen type Ialpha1 gene polymorphism in idiopathic osteoporosis in men. Rheumatology (Oxford) 39:1222–1225

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  64. Sowers M, Willing M, Burns T, Deschenes S, Hollis B, Crutchfield M, Jannausch M (1999) Genetic markers, bone mineral density and serum osteocalcin levels. J Bone Miner Res 14:1411–1419

    Article  CAS  PubMed  Google Scholar 

  65. Van Pottelbergh I, Goemaere S, Nuytinck L, De PA, Kaufman JM (2001) Association of the type I collagen alpha1 Sp1 polymorphism, bone density and upper limb muscle strength in community-dwelling elderly men. Osteoporos Int 12:895–901

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported in part by grants from the European Commission (GENOMOS; QLK6-CT-2002-02629) and from the Arthritis Research Campaign (15389).

Conflicts of interest

SHR holds patents on the use of COL1A1 genotyping as a diagnostic test for susceptibility to osteoporosis.

Author information

Authors and Affiliations

  1. Rheumatic Disease Unit, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK

    H. Jin & S. H. Ralston

  2. Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece

    E. Evangelou & J. P. A. Ioannidis

  3. Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece

    J. P. A. Ioannidis

  4. Center for Genetic Epidemiology and Modeling, ICRHPS, and Tufts Clinical and Translational Science Institute, Tufts University School of Medicine, Boston, USA

    J. P. A. Ioannidis

Authors
  1. H. Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Evangelou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. P. A. Ioannidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. H. Ralston
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. H. Ralston.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jin, H., Evangelou, E., Ioannidis, J.P.A. et al. Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies. Osteoporos Int 22, 911–921 (2011). https://doi.org/10.1007/s00198-010-1364-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-010-1364-5

Keywords

Search

Navigation