Rheumatology International

, Volume 32, Issue 5, pp 1425–1430 | Cite as

Analysis of estrogen receptor alpha gene haplotype in Mexican mestizo patients with primary osteoarthritis of the knee

  • Verónica Marusa Borgonio-Cuadra
  • Celia González-Huerta
  • Carolina Duarte-Salazár
  • María de los Ángeles Soria-Bastida
  • Socorro Cortés-González
  • Antonio Miranda-Duarte
Short Communication


The aim of this work was to test the association between estrogen receptor α gene (ERα) polymorphism and primary osteoarthritis (OA) of the knee in Mexican mestizo patients. A case–control study was conducted. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and radiologic score for OA of the knee of ≥2 according to Kellgren–Lawrence scale, and controls were subjects >40 years age with a radiologic score <2. Two restriction fragment length polymorphisms, PvuII (T/C; rs2234693), and XbaI (A/G; rs9340799), of the ERα were analyzed. Allelic haplotypes were constructed and non-conditional logistic regression was developed to evaluate risk magnitude through odds ratios (ORs) and 95% Confidence intervals (95% CI). Three different allelic haplotypes were identified: TA; CG, and CA. Unadjusted analysis of the haplotypes did not show significant associations; nonetheless, when data were adjusted for gender, age, and BMI, a significant decrease risk was observed for CG haplotype (OR [95% CI]) = 0.5 (0.3–0.9)] (P = 0.04). These results suggest that ERα gene CG haplotype could be associated with a reduced risk of primary knee OA in Mexican mestizo population.


Osteoarthritis Genetic association Polymorphism Estrogen receptor gene Haplotype 



This work was supported by a grant from the Consejo Nacional de Ciencia y Tecnología (CONACyT), México.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Felson DT (2009) Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther 11:203–213PubMedCrossRefGoogle Scholar
  2. 2.
    Spector TD, Cicuttini F, Baker J et al (1996) Genetic influences on osteoarthritis in women: a twin study. Br Med J 312:940–943CrossRefGoogle Scholar
  3. 3.
    Chitnavis J, Sinsheimer JS, Clipsham K et al (1997) Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis. J Bone Joint Surg 79:660–664CrossRefGoogle Scholar
  4. 4.
    Valdes AM, Spector TD (2008) The contribution of genes to osteoarthritis. Rheum Dis Clin North Am 34:581–603PubMedCrossRefGoogle Scholar
  5. 5.
    Spector TD, Campion GD (1989) Generalized osteoarthritis: a hormonally mediated disease. Ann Rheum Dis 48:523–527PubMedCrossRefGoogle Scholar
  6. 6.
    Zhang Y, McAlindon TE, Hannan MT et al (1998) Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study. Arthritis Rheum 41:1867–1873PubMedCrossRefGoogle Scholar
  7. 7.
    Richette P, Corvol M, Bardin T (2003) Estrogens, cartilage, and osteoarthritis. Joint Bone Spine 70:257–262PubMedCrossRefGoogle Scholar
  8. 8.
    Thornton JW (2001) Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. PNAS 98:5671–5676PubMedCrossRefGoogle Scholar
  9. 9.
    Cheung E, Schwabish MA, Kraus WL (2003) Chromatin exposes intrinsic differences in the transcriptional activities of estrogen receptors α and β. EMBO J 22:600–611PubMedCrossRefGoogle Scholar
  10. 10.
    Ponglikitmongkol M, Green S, Chambon P (1988) Genomic organization of the human oestrogen receptor gene. EMBO J 7:3385–3388PubMedGoogle Scholar
  11. 11.
    Kobayashi S, Inoue S, Hosoi T et al (1996) Association of bone mineral density with polymorphism of the estrogen receptor gene. J Bone Miner Res 11:306–311PubMedCrossRefGoogle Scholar
  12. 12.
    Ushiyama T, Ueyama H, Inoue K et al (1998) Estrogen receptor gene polymorphism and generalized osteoarthritis. J Rheumatol 25:134–137PubMedGoogle Scholar
  13. 13.
    Bergink AP, van Meurs JB, Loughlin J et al (2003) Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women. Arthritis Rheum 48:1913–1922PubMedCrossRefGoogle Scholar
  14. 14.
    Jin SY, Hong S, Yang H et al (2004) Estrogen receptors-α gene haplotypes is associated with primary knee osteoarthritis in Korean population. Arthritis Res Ther 6:415–421CrossRefGoogle Scholar
  15. 15.
    Loughlin J, Sinsheimer JS, Mustafa Z et al (2000) Association analysis of the vitamin D receptor gene, the type I collagen gene COL1A1, and the estrogen receptor gene in idiopathic osteoarthritis. J Rheumatol 27:779–784PubMedGoogle Scholar
  16. 16.
    Fytili P, Giannatou E, Papanikolaou V et al (2005) Association of repeat polymorphisms in the estrogen receptors alpha, beta, and androgen receptor genes with knee osteoarthritis. Clin Genet 68:268–277PubMedCrossRefGoogle Scholar
  17. 17.
    Lian K, Lui L, Zmuda JM et al (2007) Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women. Osteoarthritis Cartilage 15:972–978PubMedCrossRefGoogle Scholar
  18. 18.
    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502PubMedCrossRefGoogle Scholar
  19. 19.
    Davidson S, Starkey A, MacKenzie A (2009) Evidence of uneven selective pressure on different subsets of the conserved human genome; implications for the significance of intronic and intergenic DNA. BMC Genomics 10:614–620PubMedCrossRefGoogle Scholar
  20. 20.
    Wilkins JM, Southam L, Mustafa Z et al (2009) Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis (Abstract). BMC Medical Genetics 10:141PubMedCrossRefGoogle Scholar
  21. 21.
    Wang ZY, Zhang XT, Shen P et al (2005) Identification, cloning, and expression of human estrogen receptor-α36, a novel variant of human estrogen receptor-α66. Biochem Biophys Res Commun 336:1023–1027PubMedCrossRefGoogle Scholar
  22. 22.
    Herrington DM, Howard TD, Brosnihan KB et al (2009) Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein. Circulation 23(105):1879–1882Google Scholar
  23. 23.
    Hines LM, Risendal B, Slattery ML et al (2010) Comparative analysis of breast cancer risk factors among Hispanic and non-Hispanic white women. Cancer 116:3215–3223PubMedCrossRefGoogle Scholar
  24. 24.
    Nakamura T, Shi D, Tzetis M et al (2007) Meta-analysis of association between the ASPN D-repeat and osteoarthritis. Hum Mol Genet 16:1676–1681PubMedCrossRefGoogle Scholar
  25. 25.
    Cimmino MA, Parodi M (2005) Risk factors for osteoarthritis. Semin Arthritis Rheum 34(Suppl 2):29–34PubMedGoogle Scholar
  26. 26.
    Hosking L, Lumsden S, Lewis K et al (2004) Detection of genotyping errors by Hardy-Weinberg equilibrium testing. Eur J Hum Genet 12:395–399PubMedCrossRefGoogle Scholar
  27. 27.
    Herrero-Beaumont G, Román-Blás JA, Castañeda S et al (2009) Primary osteoarthritis no longer primary: three subsets with distinct etiological, clinical, and therapeutic characteristics. Semin Arthritis Rheum 39:71–80PubMedCrossRefGoogle Scholar
  28. 28.
    Spector TD, Hochberg MC (1994) Methodological problems in the epidemiological study of osteoarthritis. Ann Rheum Dis 53:143–146PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Verónica Marusa Borgonio-Cuadra
    • 1
  • Celia González-Huerta
    • 1
  • Carolina Duarte-Salazár
    • 2
  • María de los Ángeles Soria-Bastida
    • 3
  • Socorro Cortés-González
    • 4
  • Antonio Miranda-Duarte
    • 1
  1. 1.Departamento de GenéticaInstituto Nacional de Rehabilitación (INR)MéxicoMéxico
  2. 2.Servicio de ReumatologíaInstituto Nacional de Rehabilitación (INR)MéxicoMéxico
  3. 3.Servicio de Rehabilitación ArticularInstituto Nacional de Rehabilitación (INR)MéxicoMéxico
  4. 4.Servicio de Resonancia MagnéticaInstituto Nacional de Rehabilitación (INR)MéxicoMéxico

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