Skip to main content
SpringerLink
Log in

The D-repeat polymorphism in the ASPN gene and primary knee osteoarthritis in a Mexican mestizo population: a case–control study

  • Original Article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

A genetic association between osteoarthritis (OA) and a polymorphism in the aspartic acid (D) repeat of the asporin (ASPN) gene has been reported in Japanese, Han Chinese, Greek and UK Caucasian populations of patients having knee and hip OA. Such an association has not been previously described among the Mexican mestizo population. The aim of this study was to analyze the association of the ASPN gene D-repeat polymorphism in a Mexican mestizo population with primary knee OA as well as in healthy controls.

Materials and methods

A case–control study was conducted on a Mexican mestizo population of northern Mexico. The repeat polymorphism was genotyped in 440 subjects (218 cases and 222 healthy controls). Primary knee OA was diagnosed according to American College of Rheumatology and Kellgren-Lawrence criteria, and allelic association was examined adjusting for other risk variables.

Results

After adjusting for some covariates, menopause and the D16 allele showed a trend toward being risk factors for knee OA in a Mexican mestizo population. Also, the D12 allele could be considered as a protective factor.

Conclusions

These findings suggest that polymorphisms within the ASPN gene could influence knee OA susceptibility, but these associations must be confirmed by independent studies in larger samples and different ethnic groups to support the role of the D-repeat polymorphism in the ASPN gene as risk or protection factors for knee OA in a Mexican 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

Similar content being viewed by others

References

  1. Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133:635–46.

    Article  PubMed  CAS  Google Scholar 

  2. Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D. Genetic influences on osteoarthritis in women: a twin study. BMJ. 1996;312:940–3.

    Article  PubMed  CAS  Google Scholar 

  3. Bijkerk C, Houwing-Duistermaat JJ, Valkenburg HA, Meulenbelt I, Hofman A, Breedveld FC, Huibert A, Pols P, Van Duijn CM, Eline Slagboom P. Heritabilities of radiologic osteoarthritis in peripheral joints and of disc degeneration of the spine. Arthr Rheum. 1999;42:1729–35.

    Article  CAS  Google Scholar 

  4. Hirsch R, Lethbridge-Cejku M, Hanson R, Scott WW Jr, Reichle R, Plato CC, Tobin Jordan D, Hochberg MC. Familial aggregation of osteoarthritis: data from the Baltimore longitudinal study on aging. Arthr Rheum. 1998;41:1227–32.

    Article  CAS  Google Scholar 

  5. Sakao K, Takahashi KA, Arai Y, Saito M, Honjyo K, Hiraoka N, Kishida T, Mazda O, Imanishi J, Kubo T. Asporin and transforming growth factor-beta gene expression in osteoblasts from subchondral bone and osteophytes in osteoarthritis. J Orthop Sci. 2009;14:738–47.

    Article  PubMed  CAS  Google Scholar 

  6. Gill MR, Oldberg A, Reinholt FP. Fibromodulin-null murine knee joints display increased incidences of osteoarthritis and alterations in tissue biochemistry. Osteoarthr Cartil. 2002;10:751–7.

    Article  PubMed  CAS  Google Scholar 

  7. Kizawa H, Kou I, Iida A, Sudo A, Miyamoto Y, Fukuda A, Mabuchi A, Kotani A, Kawakami A, Yamamoto S, Uchida A, Nakamura K, Notoya K, Nakamura Y, Ikegawa S. An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet. 2005;37:138–44.

    Article  PubMed  CAS  Google Scholar 

  8. Jiang Q, Shi D, Yi L, Ikegawa S, Wang Y, Nakamura T, Qiao D, Liu C, Dai J. Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese. J Hum Genet. 2006;51:1068–72.

    Article  PubMed  CAS  Google Scholar 

  9. Kaliakatsos M, Tzetis M, Kanavakis E, Fytili P, Chouliaras G, Karachalios T, Malizos K, Tsezou A. Asporin and knee osteoarthritis in patients of Greek origin. Osteoarthr Cartil. 2006;14:609–11.

    Article  PubMed  CAS  Google Scholar 

  10. Mustafa Z, Dowling B, Chapman K, Sinsheimer JS, Carr A, Loughlin J. Investigating the aspartic acid (D) repeat of asporin as a risk factor for osteoarthritis in a UK Caucasian population. Arthr Rheum. 2005;52:3502–6.

    Article  CAS  Google Scholar 

  11. Nakamura T, Shi D, Tzetis M, Rodriguez-Lopez J, Miyamoto Y, Tsezou A, Gonzalez A, Jiang Q, Kamatani N, Loughlin J, Ikegawa S. Meta-analysis of association between the ASPN D-repeat and osteoarthritis. Hum Mol Genet. 2007;16:1676–81.

    Article  PubMed  CAS  Google Scholar 

  12. Rodriguez-Amado J, Pelaez-Ballestas I, Sanin LH, Esquivel-Valerio JA, Burgos-Vargas R, Perez-Barbosa L, Riega-Torres J, Garza-Elizondo MA. Epidemiology of rheumatic diseases. A community-based study in urban and rural populations in the state of Nuevo Leon, Mexico. J Rheumatol Suppl. 2011;86:9–14.

    Article  PubMed  Google Scholar 

  13. Nakajima M, Kizawa H, Saitoh M, Kou I, Miyazono K, Ikegawa S. Mechanisms for asporin function and regulation in articular cartilage. J Biol Chem. 2007;282:32185–92.

    Article  PubMed  CAS  Google Scholar 

  14. Lorenzo P, Aspberg A, Onnerfjord P, Bayliss MT, Neame PJ, Heinegard D. Identification and characterization of asporin. a novel member of the leucine-rich repeat protein family closely related to decorin and biglycan. J Biol Chem. 2001;276:12201–11.

    Article  PubMed  CAS  Google Scholar 

  15. Kou I, Nakajima M, Ikegawa S. Binding characteristics of the osteoarthritis-associated protein asporin. J Bone Miner Metab. 2010;28:395–402.

    Article  PubMed  CAS  Google Scholar 

  16. Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, Brown C, Cooke TD, Daniel W, Gray R. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthr Rheum. 1990;33:1601–10.

    Article  CAS  Google Scholar 

  17. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthr Rheum. 1986;29:1039–49.

    Article  CAS  Google Scholar 

  18. Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, Brown C, Cooke TD, Daniel W, Feldman D. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthr Rheum. 1991;34:505–14.

    Article  CAS  Google Scholar 

  19. Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis. 1957;16:494–502.

    Article  PubMed  CAS  Google Scholar 

  20. Iqbal MN, Haidri FR, Motiani B, Mannan A. Frequency of factors associated with knee osteoarthritis. J Pak Med Assoc. 2011;61:786–9.

    PubMed  Google Scholar 

  21. Spector TD, MacGregor AJ. Risk factors for osteoarthritis: genetics. Osteoarthr Cartil. 2004;12(Suppl A):S39–44.

    Article  PubMed  Google Scholar 

  22. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  PubMed  CAS  Google Scholar 

  23. Torres B, Orozco G, Garcia-Lozano JR, Oliver J, Fernandez O, Gonzalez-Gay MA, Balsa A, García A, Pascual-Salcedo D, López-Nevot MA, Núñez-Roldán A, Martín J, González-Escribano MF. Asporin repeat polymorphism in rheumatoid arthritis. Ann Rheum Dis. 2007;66:118–20.

    Article  PubMed  CAS  Google Scholar 

  24. Atif U, Philip A, Aponte J, Woldu EM, Brady S, Kraus VB, Jordan JM, Doherty M, Wilson AG, Moskowitz RW, Hochberg M, Loeser R, Renner JB, Chiano M. Absence of association of asporin polymorphisms and osteoarthritis susceptibility in US Caucasians. Osteoarthr Cartil. 2008;16:1174–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Gabriela Salinas Medina from the Instituto de Ciencia y Medicina Genómica Torreón, Mexico, for her technical support; Ignacio Rego Pérez from Instituto de Investigación Biomédica (INIBIC) A Coruña, Spain, for his statistical analysis support; Pablo Ruiz Flores, and María Elena Cortéz and Francisco Carlos Lopez Marquez from the Centro de Investigación Biomédica Torreón, Mexico, for their review of the manuscript. We would also like to thank Juanita Oropeza, Rubén Dario Galvan, Claudia Hernandez Vallejo, René Rodriguez and Eduardo Serna Zetina from Facultad de Medicina, Torreón, Mexico, for their invaluable logistical and administrative support. This study was funded by the Facultad de Medicina Torreón, Universidad Autónoma de Coahuila, Mexico, and Instituto de Ciencia y Medicina Genómica, Torreón, Mexico. The study sponsors had no involvement in the study design, collection, analysis and interpretation of data or the decision to submit this manuscript for publication.

Conflict of interest

The authors declare that they have no competing interests that could potentially and inappropriately influence their work and conclusions.

Author information

Authors and Affiliations

  1. Facultad de Medicina Torreón, Universidad Autónoma de Coahuila, Avenida Morelos 900 Oriente C.P. 27000, Torreón, Coahuila, Mexico

    R. D. Arellano, V. M. Velasco & J. R. Arguello

  2. Instituto de Ciencia y Medicina Genómica, Torreón, Coahuila, Mexico

    R. D. Arellano, F. Hernández, C. R. Loera & J. R. Arguello

  3. Facultad de Ciencias Biológicas, Universidad Autónoma de Coahuila, Torreón, Coahuila, Mexico

    F. Hernández

  4. Laboratorio de Genómica Viral y Humana, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico

    C. A. García-Sepúlveda

  5. Escuela de Enfermería, Universidad Autónoma de Coahuila, Torreón, Coahuila, Mexico

    V. M. Velasco

Authors
  1. R. D. Arellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. A. García-Sepúlveda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. M. Velasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. R. Loera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. R. Arguello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. D. Arellano.

About this article

Cite this article

Arellano, R.D., Hernández, F., García-Sepúlveda, C.A. et al. The D-repeat polymorphism in the ASPN gene and primary knee osteoarthritis in a Mexican mestizo population: a case–control study. J Orthop Sci 18, 826–831 (2013). https://doi.org/10.1007/s00776-013-0414-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00776-013-0414-1

Keywords

Search

Navigation