A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

Lara Bossini-Castillo, Jasper C. A. Broen, Carmen P. Simeon, Lorenzo Beretta, Madelon C. Vonk, Norberto Ortego-Centeno, Gerard Espinosa, Patricia Carreira, Maria Teresa Camps, Nuria Navarrete, Maria F. Gonzalez-Escribano, Esther Vicente-Rabaneda, Luis Rodriguez, Carlos Tolosa, Jose A. Roman-Ivorra, Inmaculada Gomez-Gracia, Francisco J. Garcia-Hernandez, Ivan Castellvi, Maria Gallego, Antonio Fernandez-NebroRosa Garcia-Portales, Maria Victoria Egurbide, Vicente Fonollosa, Paloma Garcia de la Pena, Ana Pros, Miguel A. Gonzalez-Gay, Roger Hesselstrand, Gabriela Riemekasten, Torsten Witte, Marieke J. H. Coenen, Bobby P. Koeleman, Frederic Houssiau, Vanessa Smith, Filip de Keyser, Rene Westhovens, Ellen De Langhe, Alexandre E. Voskuyl, Annemie J. Schuerwegh, Meng May Chee, Rajan Madhok, Paul Shiels, Carmen Fonseca, Christopher Denton, Kathleen Claes, Leonid Padykov, Annika Nordin, Oyvind Palm, Benedicte A. Lie, Paolo Airo, Raffaella Scorza, Jacob M. van Laar, Nicolas Hunzelmann, Alexander Kreuter, Ariane Herrick, Jane Worthington, Timothy R. D. J. Radstake, Javier Martin, Blanca Rueda

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Objectives The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. 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. 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). Conclusions The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
Original languageEnglish
Pages (from-to)638-641
JournalAnnals of the Rheumatic Diseases
Issue number4
Publication statusPublished - 2011

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity


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