LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Bossini-Castillo, L.; Broen, J.C.A.; Simeon, C.P.; Beretta, L.; Vonk, M.C.; Ortego-Centeno, N.; Espinosa, G.; Carreira, P.; Camps, M.T.; Navarrete, N.; Gonzalez-Escribano, M.F.; Vicente-Rabaneda, E.; Rodriguez, L.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Gracia, I.; Garcia-Hernandez, F.J.; Castellvi, I.; Gallego, M.; Fernandez-Nebro, A.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; de la Pena, P.G.; Pros, A.; Gonzalez-Gay, M.A.; Hesselstrand, R.; Riemekasten, G.; Witte, T.; Coenen, M.J.H. ... view all 58 authors View less authors (2011)
Publisher: B M J Group
Languages: English
Types: Article
Subjects:

Objectives The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.

\ud \ud

Methods A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.

\ud \ud

Results A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).

\ud \ud

Conclusions The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.

  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Steen VD. The many faces of scleroderma. Rheum Dis Clin North Am 2008;34:1-15; v.
    • 2. Agarwal SK, Tan FK, Arnett FC. Genetics and genomic studies in scleroderma (systemic sclerosis). Rheum Dis Clin North Am 2008;34:17-40; v.
    • 3. Agarwal SK, Reveille JD. The genetics of scleroderma (systemic sclerosis). Curr Opin Rheumatol 2010;22:133-8.
    • 4. Zhou X, Lee JE, Arnett FC, et al. HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans. Arthritis Rheum 2009;60:3807-14.
    • 5. Radstake TR, Gorlova O, Rueda B, et al. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet 2010;42:426-9.
    • 6. Gourh P, Arnett FC, Tan FK, et al. Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. Ann Rheum Dis 2010;69:550-5.
    • 7. Manku H, Graham DS, Vyse TJ. Association of the co-stimulator OX40L with systemic lupus erythematosus. J Mol Med 2009;87:229-34.
    • 8. Gough MJ, Weinberg AD. OX40 (CD134) and OX40L. Adv Exp Med Biol 2009;647:94-107.
    • 9. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 1980;23:581-90.
    • 10. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15:202-5.
    • 11. Skol AD, Scott LJ, Abecasis GR, et al. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 2006;38:209-13.
    • 12. Cunninghame Graham DS, Graham RR, Manku H, et al. Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nat Genet 2008;40:83-9.
    • 13. Delgado-Vega AM, Abelson AK, S├ínchez E, et al. Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus. Genes Immun 2009;10:248-53.
    • 14. Croft M. Control of immunity by the TNFR-related molecule OX40 (CD134). Annu Rev Immunol 2010;28:57-78.
    • 15. Croft M, So T, Duan W, et al. The significance of OX40 and OX40L to T-cell biology and immune disease. Immunol Rev 2009;229:173-91.
    • 16. Radstake TR, van Bon L, Broen J, et al. Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFbeta expression. PLoS ONE 2009;4:e5981.
  • No related research data.
  • No similar publications.

Share - Bookmark

Download from

Cite this article