Skip to main content
SpringerLink
Log in

Association of ADAM 12 polymorphisms with the risk of knee osteoarthritis: meta-analysis of 5048 cases and 6848 controls

  • Genes and Disease
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Several studies have suggested the association between ADAM 12 polymorphisms and the risk of osteoarthritis (OA), but the results remained controversial. Therefore, we designed a meta-analysis to systematically evaluate the association on this issue. A literature search for eligible studies was conducted in PubMed, Web of Science and Google Scholar databases. The association between ADAM 12 polymorphisms and knee OA risk was calculated by odds ratios (ORs) and 95% confidence intervals (CIs). Study heterogeneity, sensitivity and publication bias analyses were also conducted. Ten articles covering 5048 cases and 6848 controls met our criteria for the final analysis. We found that the rs1871054 was significantly associated with the risk of knee OA (allele model OR 1.72, 95% CI 1.43–2.07, P < 0.001; additive model: OR 2.06, 95% CI 1.19–3.56, P = 0.010; dominant model: OR 2.45, 95% CI 1.85–3.25, P < 0.001; recessive model: OR 1.54, 95% CI 1.13–2.10, P = 0.007). rs1044122 was significantly associated with knee OA susceptibility in recessive model (OR 1.45, 95% CI 1.03–2.04, P = 0.031). For rs3740199 and rs1278279, no significant associations with knee OA were found. In the stratified analysis by gender, significant association was identified with the risk of knee OA for rs3740199 in men in allele model (OR 2.41, 95% CI 1.51–3.84, P < 0.001), dominant model (OR 2.68, 95% CI 1.17–6.14, P = 0.02) and recessive model (OR 3.51, 95% CI 1.68–7.36, P = 0.001), but not for additive model (OR 1.30, 95% CI 0.81–2.08, P = 0.28). This meta-analysis suggests that the ADAM 12 genetic polymorphisms rs1871054 and rs1044122 might be associated with risk of knee OA; rs3740199 might be associated with risk of knee OA in men. Further well-designed and large scale studies are warranted to validate these associations.

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

Similar content being viewed by others

References

  1. Tonge DP, Pearson MJ, Jones SW (2014) The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics. Osteoarthr Cartil 22(5):609–621

    Article  CAS  PubMed  Google Scholar 

  2. Peat G, McCarney R, Croft P (2001) Knee pain and osteoarthritis in older adults: a review of the community burden and current use of primary health care. Ann Rheum Dis 60(2):91–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Brandt KD, Dieppe P, Radin E (2009) Etiopathogenesis of osteoarthritis. Med Clin North Am 93(1):1–24

    Article  PubMed  Google Scholar 

  4. Zintzaras E, Kitsios GD, Ziogas DC, Rodopoulou P, Karachalios T (2010) Field synopsis and synthesis of genetic association studies in osteoarthritis: the CUMAGAS-OSTEO information system. Am J Epidemiol 171(8):851–858

    Article  PubMed  Google Scholar 

  5. Malemud C, Muoh O, Askari A (2014) Clinical significance and implications of genetic and genomic studies in patients with osteoarthritis. Adv Genom Genet 4:193–206

    Article  Google Scholar 

  6. Yang CY, Chanalaris A, Troeberg L (2017) ADAMTS and ADAM metalloproteinases in osteoarthritis-looking beyond the ‘usual suspects’. Osteoarthr Cartil 25(7):1000–1009

    Article  PubMed  PubMed Central  Google Scholar 

  7. Aigner T, Soeder S, Haag J (2006) IL-1beta and BMPs-interactive players of cartilage matrix degradation and regeneration. Eur Cell Mater 12:49–56 (discussion 56)

    Article  CAS  PubMed  Google Scholar 

  8. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology. J Am Med Assoc 283(15):2008–2012

    Article  CAS  Google Scholar 

  9. Cao JL, Yuan P, Abuduwufuer A, Lv W, Yang YH, Hu J (2015) Association between the TERT genetic polymorphism rs2853676 and cancer risk: meta-analysis of 76,108 cases and 134,215 controls. PLoS One 10(6):e0128829

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    CAS  PubMed  Google Scholar 

  11. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  12. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  PubMed Central  Google Scholar 

  13. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Valdes AM, Hart DJ, Jones KA, Surdulescu G, Swarbrick P, Doyle DV, Schafer AJ, Spector TD (2004) Association study of candidate genes for the prevalence and progression of knee osteoarthritis. Arthritis Rheum 50(8):2497–2507

    Article  CAS  PubMed  Google Scholar 

  15. Valdes AM, Van Oene M, Hart DJ, Surdulescu GL, Loughlin J, Doherty M, Spector TD (2006) Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women. Arthritis Rheum 54(2):533–539

    Article  CAS  PubMed  Google Scholar 

  16. Kerna I, Kisand K, Tamm AE, Lintrop M, Veske K, Tamm AO (2009) Missense single nucleotide polymorphism of the ADAM12 gene is associated with radiographic knee osteoarthritis in middle-aged Estonian cohort. Osteoarthr Cartil 17(8):1093–1098

    Article  CAS  PubMed  Google Scholar 

  17. Limer KL, Tosh K, Bujac SR, McConnell R, Doherty S, Nyberg F, Zhang W, Doherty M, Muir KR, Maciewicz RA (2009) Attempt to replicate published genetic associations in a large, well-defined osteoarthritis case–control population (the GOAL study). Osteoarthr Cartil 17(6):782–789

    Article  CAS  PubMed  Google Scholar 

  18. Rodriguez-Lopez J, Pombo-Suarez M, Loughlin J, Tsezou A, Blanco FJ, Meulenbelt I, Slagboom PE, Valdes AM, Spector TD, Gomez-Reino JJ, Gonzalez A (2009) Association of a nsSNP in ADAMTS14 to some osteoarthritis phenotypes. Osteoarthr Cartil 17(3):321–327

    Article  CAS  PubMed  Google Scholar 

  19. Shin MH, Lee SJ, Kee SJ, Song SK, Kweon SS, Park DJ, Park YW, Lee SS, Kim TJ (2012) Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis. Jt Bone Spine 79(5):488–491

    Article  CAS  PubMed  Google Scholar 

  20. Kerna I, Kisand K, Tamm AE, Kumm J, Tamm AO (2013) Two single-nucleotide polymorphisms in ADAM12 gene are associated with early and late radiographic knee osteoarthritis in Estonian population. Arthritis 2013:878126

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lou S, Zhao Z, Qian J, Zhao K, Wang R (2014) Association of single nucleotide polymorphisms in ADAM12 gene with susceptibility to knee osteoarthritis: a case-control study in a Chinese Han population. Int J Clin Exp Pathol 7(8):5154–5159

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang L, Guo L, Tian F, Hao R, Yang T (2015) Analysis of single nucleotide polymorphisms within ADAM12 and risk of knee osteoarthritis in a Chinese Han population. Biomed Res Int 2015:518643

    PubMed  PubMed Central  Google Scholar 

  23. Poonpet T, Tammachote R, Tammachote N, Kanitnate S, Honsawek S (2016) Association between ADAM12 polymorphism and knee osteoarthritis in Thai population. Knee 23(3):357–361

    Article  PubMed  Google Scholar 

  24. Takahashi H, Nakajima M, Ozaki K, Tanaka T, Kamatani N, Ikegawa S (2010) Prediction model for knee osteoarthritis based on genetic and clinical information 2010. Arthritis Res Ther 12(5):R187

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zeggini E, Panoutsopoulou K, Southam L, Rayner NW, Day-Williams AG, Lopes MC et al (2012) Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study. Lancet 380(9844):815–823

    Article  PubMed  Google Scholar 

  26. Evangelou E, Valdes AM, Kerkhof HJ, Styrkarsdottir U, Zhu Y, Meulenbelt I et al (2011) Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Ann Rheum Dis 70(2):349–355

    Article  CAS  PubMed  Google Scholar 

  27. Mao X, Ke Z, Liu S, Tang B, Wang J, Huang H, Chen S (2015) IL-1β +3953C/T, −511T/C and IL-6 −174C/G polymorphisms in association with tuberculosis susceptibility: a meta-analysis. Gene 573(1):75–83

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedics, The Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 318, Chaowang Road, Hangzhou, 310005, Zhejiang, People’s Republic of China

    Xuerong Hu, Guoli Sun & Weidong Wang

Authors
  1. Xuerong Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guoli Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weidong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weidong Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Funding

This study was funded by the Natural Science Foundation of Zhejiang Province, China (Grant number LY13H270007).

Conflict of interest

Xuerong Hu, Guoli Sun and Weidong Wang declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, X., Sun, G. & Wang, W. Association of ADAM 12 polymorphisms with the risk of knee osteoarthritis: meta-analysis of 5048 cases and 6848 controls. Rheumatol Int 37, 1659–1666 (2017). https://doi.org/10.1007/s00296-017-3778-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-017-3778-2

Keywords

Search

Navigation