Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Jaap Van Laar


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.

Publication metadata

Author(s): Bossini-Castillo L, Broen JCA, Simeon CP, Beretta L, Vonk MC, Ortego-Centeno N, Espinosa G, Carreira P, Camps MT, Navarrete N, Gonzalez-Escribano MF, Vicente-Rabaneda E, Rodriguez L, Tolosa C, Roman-Ivorra JA, Gomez-Gracia I, Garcia-Hernandez FJ, Castellvi I, Gallego M, Fernandez-Nebro A, Garcia-Portales R, Egurbide MV, Fonollosa V, de la Pena PG, Pros A, Gonzalez-Gay MA, Hesselstrand R, Riemekasten G, Witte T, Coenen MJH, Koeleman BP, Houssiau F, Smith V, de Keyser F, Westhovens R, De Langhe E, Voskuyl AE, Schuerwegh AJ, Chee MM, Madhok R, Shiels P, Fonseca C, Denton C, Claes K, Padykov L, Nordin A, Palm O, Lie BA, Airo P, Scorza R, van Laar JM, Hunzelmann N, Kreuter A, Herrick A, Worthington J, Radstake TRDJ, Martin J, Rueda B

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2011

Volume: 70

Issue: 4

Pages: 638-641

Print publication date: 27/12/2010

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

Publisher: BMJ Publishing Group


DOI: 10.1136/ard.2010.141838


Altmetrics provided by Altmetric


Funder referenceFunder name
Dutch arthritis foundation (National Reumafonds)
Dutch association of research (NOW)
FWO Vlaanderen (Flanders Research Foundation)
CTS-180Junta de Andalucia
CTS-4977Junta de Andalucia
RD08/0075Instituto de Salud Carlos III (ISCIII)