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Extended report
Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis
  1. Pravitt Gourh1,
  2. Frank C Arnett1,
  3. Filemon K Tan1,
  4. Shervin Assassi1,
  5. Dipal Divecha1,
  6. Gene Paz1,
  7. Terry McNearney2,
  8. Hilda Draeger3,
  9. John D Reveille1,
  10. Maureen D Mayes1,
  11. Sandeep K Agarwal1
  1. 1Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTHSC-H), Houston, Texas, USA
  2. 2University of Texas Medical Branch at Galveston, Galveston, Texas, USA
  3. 3University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  1. Correspondence to Dr Sandeep K Agarwal, Division of Rheumatology and Clinical Immunogenetics, 6431 Fannin Street, MSB 5.278, Houston, Texas 77030, USA; sandeep.k.agarwal{at}


Objective It is increasingly being appreciated that multiple autoimmune diseases share common susceptibility genes. The tumour necrosis factor ligand superfamily member 4 gene (TNFSF4, OX40L), which encodes for the T cell costimulatory molecule OX40 ligand, has been identified as a susceptibility gene for the development of systemic lupus erythematosus (SLE). Accordingly, the aim of the current study was to investigate the possible association of the TNFSF4 gene region with systemic sclerosis (SSc), an autoimmune disease that leads to the development of cutaneous and visceral fibrosis.

Methods A total of 9 single nucleotide polymorphisms (SNPs) in the TNFSF4 gene region, previously associated with susceptibility to SLE, were tested for association with SSc in a collection of 1059 patients with SSc and 698 controls.

Results Case-control comparisons revealed a significant association between susceptibility to SSc and the minor alleles at SNPs rs1234314 (OR 1.20, 95% CI 1.04 to 1.4, pFDR=0.019), rs2205960 (OR 1.24, 95% CI 1.10 to 1.50, pFDR=0.019) and rs844648 (OR 1.16, 95% CI 1.01 to 1.30, pFDR=0.032). The minor allele at rs844644 was protective (OR 0.84, 95% CI 0.70 to 0.97, pFDR=0.038). Analysis of subsets of patients with SSc demonstrated significant associations of the TNFSF4 SNPs with limited and diffuse SSc as well as specific SNPs that were associated with SSc-associated autoantibodies. Finally, the analyses suggest a potential interaction between two TNFSF4 SNPs, rs2205960 and rs844648, with regards to SSc susceptibility.

Conclusions Polymorphisms in the TNFSF4 gene region are associated with susceptibility to SSc and its clinical and autoantibody subsets. TNFSF4 may be another gene that confers risk to multiple autoimmune diseases.

This paper is freely available online under the BMJ Journals unlocked scheme, see

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  • Web Only Data ard.2009.116434

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  • Ethics approval This study was conducted with the approval of the University of Texas Health Science Center at Houston Medical School IRB (Committee for the Protection of Human Subjects).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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