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Association of TNFSF4 (OX40L) polymorphisms with susceptibility to Systemic Sclerosis
  1. Pravitt Gourh (pravitt.gourh{at}uth.tmc.edu)
  1. The University of Texas Health Science Center at Houston, United States
    1. Frank C Arnett (frank.c.arnett{at}uth.tmc.edu)
    1. The University of Texas Health Science Center at Houston, United States
      1. Filemon K Tan (filemon.k.tan{at}uth.tmc.edu)
      1. The University of Texas Health Science Center at Houston, United States
        1. Shervin Assassi (shervin.assassi{at}uth.tmc.edu)
        1. The University of Texas Health Science Center at Houston, United States
          1. Dipal Divecha
          1. The University of Texas Health Science Center at Houston, United States
            1. Gene Paz
            1. The University of Texas Health Science Center at Houston, United States
              1. Terry McNearney
              1. The University fo Texas Medical Branch - Galveston, United States
                1. Hilda Draeger
                1. University of Texas Health Science Center at San Antonio, United States
                  1. John D Reveille (john.d.reveille{at}uth.tmc.edu)
                  1. The University of Texas Health Science Center at Houston, United States
                    1. Maureen D Mayes (maureen.d.mayes{at}uth.tmc.edu)
                    1. The University of Texas Health Science Center at Houston, United States
                      1. Sandeep K Agarwal (sandeep.k.agarwal{at}uth.tmc.edu)
                      1. The University of Texas Health Science Center at Houston, United States

                        Abstract

                        Objective: It is increasingly being appreciated that multiple autoimmune diseases share common susceptibility genes. TNFSF4, 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: We tested 9 single nucleotide polymorphisms (SNPs) in the TNFSF4 gene region, previously associated with susceptibility to SLE, for association with SSc in a collection of 1059 SSc cases 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 1.04-1.4, PFDR=0.019), rs2205960 (OR 1.24, 95%CI 1.10-1.50, PFDR=0.019), and rs844648 (OR 1.16, 95%CI 1.01-1.30, PFDR=0.032). The minor allele at rs844644 was protective (OR 0.84, 95%CI 0.70-0.97, PFDR=0.038). Analysis of subsets of SSc patients demonstrated significant associations of the TNFSF4 SNPs with both 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.

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