Osteoporosis International

, Volume 22, Issue 3, pp 911–921 | Cite as

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

  • H. Jin
  • E. Evangelou
  • J. P. A. Ioannidis
  • S. H. Ralston
Original Article



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.


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.


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.


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.


BMD COL1A1 Fracture Genetic Meta-analysis Osteoporosis Polymorphism 



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.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • H. Jin
    • 1
  • E. Evangelou
    • 2
  • J. P. A. Ioannidis
    • 2
    • 3
    • 4
  • S. H. Ralston
    • 1
  1. 1.Rheumatic Disease Unit, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General HospitalUniversity of EdinburghEdinburghUK
  2. 2.Clinical and Molecular Epidemiology Unit, Department of Hygiene and EpidemiologyUniversity of Ioannina School of MedicineIoanninaGreece
  3. 3.Biomedical Research Institute, Foundation for Research and Technology-HellasIoanninaGreece
  4. 4.Center for Genetic Epidemiology and Modeling, ICRHPS, and Tufts Clinical and Translational Science InstituteTufts University School of MedicineBostonUSA

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