TY - JOUR T1 - A replication study confirms the association of <em>TNFSF4 (OX40L)</em> polymorphisms with systemic sclerosis in a large European cohort JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 638 LP - 641 DO - 10.1136/ard.2010.141838 VL - 70 IS - 4 AU - Lara Bossini-Castillo AU - Jasper C A Broen AU - Carmen P Simeon AU - Lorenzo Beretta AU - Madelon C Vonk AU - Norberto Ortego-Centeno AU - Gerard Espinosa AU - Patricia Carreira AU - María Teresa Camps AU - Nuria Navarrete AU - María F González-Escribano AU - Esther Vicente-Rabaneda AU - Luis Rodríguez AU - Carlos Tolosa AU - José A Román-Ivorra AU - Inmaculada Gómez-Gracia AU - Francisco J García-Hernández AU - Iván Castellví AU - María Gallego AU - Antonio Fernández-Nebro AU - Rosa García-Portales AU - María Victoria Egurbide AU - Vicente Fonollosa AU - Paloma García de la Peña AU - Ana Pros AU - Miguel A González-Gay AU - Roger Hesselstrand AU - Gabriela Riemekasten AU - Torsten Witte AU - Marieke J H Coenen AU - Bobby P Koeleman AU - Frederic Houssiau AU - Vanessa Smith AU - Filip de Keyser AU - Rene Westhovens AU - Ellen De Langhe AU - Alexandre E Voskuyl AU - Annemie J Schuerwegh AU - Meng May Chee AU - Rajan Madhok AU - Paul Shiels AU - Carmen Fonseca AU - Christopher Denton AU - Kathleen Claes AU - Leonid Padykov AU - Annika Nordin AU - Øyvind Palm AU - Benedicte A Lie AU - Paolo Airó AU - Raffaella Scorza AU - Jacob M van Laar AU - Nicolas Hunzelmann AU - Alexander Kreuter AU - Ariane Herrick AU - Jane Worthington AU - Timothy R D J Radstake AU - Javier Martín AU - Blanca Rueda Y1 - 2011/04/01 UR - http://ard.bmj.com/content/70/4/638.abstract N2 - 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. ER -