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, María Teresa Camps, Nuria Navarrete, María F. González-Escribano, Esther Vicente-Rabaneda, Luis Rodríguez, Carlos Tolosa, José A. Román-Ivorra, Inmaculada Gómez-Gracia, Francisco J. García-Hernández, Iván Castellví, María Gallego, Antonio Fernández-NebroRosa García-Portales, María Victoria Egurbide, Vicente Fonollosa, Paloma García De La Peña, Ana Pros, Miguel A. González-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, Øyvind Palm, Benedicte A. Lie, Paolo Airó, Raffaella Scorza, Jacob M. Van Laar, Nicolas Hunzelmann, Alexander Kreuter, Ariane Herrick, Jane Worthington, Timothy R.D.J. Radstake, Javier Martín, Blanca Rueda*

*Corresponding author for this work
55 Citations (Scopus)


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 anticentromere 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
JournalAnnals of the Rheumatic Diseases
Issue number4
Pages (from-to)638-641
Number of pages4
Publication statusPublished - 04.2011

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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