Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar;69(3):550-5.
doi: 10.1136/ard.2009.116434. Epub 2009 Sep 23.

Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis

Pravitt Gourh  1 , Frank C Arnett, Filemon K Tan, Shervin Assassi, Dipal Divecha, Gene Paz, Terry McNearney, Hilda Draeger, John D Reveille, Maureen D Mayes, Sandeep K Agarwal
Affiliations

Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis

Pravitt Gourh et al. Ann Rheum Dis. 2010 Mar.

Erratum in

  • Ann Rheum Dis. 2011 May;70(5):880

Abstract

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, p(FDR)=0.019), rs2205960 (OR 1.24, 95% CI 1.10 to 1.50, p(FDR)=0.019) and rs844648 (OR 1.16, 95% CI 1.01 to 1.30, p(FDR)=0.032). The minor allele at rs844644 was protective (OR 0.84, 95% CI 0.70 to 0.97, p(FDR)=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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Linkage disequilibrium (LD) and haplotype block structure of the tumour necrosis factor ligand superfamily member 4 gene (TNFSF4) within healthy controls. Blocks connecting pairs of single nucleotide polymorphisms (SNPs) are shaded according to the strength of the linkage disequilibrium between the SNPs, from 0.0 (white) to 1.0 (black), as measured by the disequilibrium coefficient D’. As an additional measure of strength of LD, r values are given as numerical values within each box.
Figure 2
Figure 2
Estimated risk of the tumour necrosis factor ligand superfamily member 4 gene (TNFSF4) single nucleotide polymorphisms (SNPs) in systemic sclerosis (SSc) and subsets of SSc compared to controls by logistic regression controlling for gender.
Figure 3
Figure 3
Cartesian and regression tree analysis (CART) showing an interaction between the tumour necrosis factor ligand superfamily member 4 gene (TNFSF4) single nucleotide polymorphisms (SNPs) rs2205960 and rs944648 in systemic sclerosis (SSc). Red test result denotes SSc susceptibility factors.
See this image and copyright information in PMC

References

    1. Plenge RM, Padyukov L, Remmers EF, et al. Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Am J Hum Genet 2005;77:1044–60 - PMC - PubMed
    1. Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009;360:1646–54 - PubMed
    1. Harley IT, Kaufman KM, Langefeld CD, et al. Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet 2009;10:285–90 - PMC - PubMed
    1. Begovich AB, Carlton VE, Honigberg LA, et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 2004;75:330–7 - PMC - PubMed
    1. Onengut-Gumuscu S, Ewens KG, Spielman RS, et al. A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes Immun 2004;5:678–80 - PubMed

Publication types