Open Access Open Badges Research article

Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

María Teruel1*, Carmen P Simeon2, Jasper Broen3, Madelon C Vonk3, Patricia Carreira4, Maria Teresa Camps5, Rosa García-Portales6, Esmeralda Delgado-Frías7, Maria Gallego8, Gerard Espinosa9, the Spanish Scleroderma Group10, Lorenzo Beretta11, Paolo Airó12, Claudio Lunardi13, Gabriela Riemekasten14, Torsten Witte15, Thomas Krieg16, Alexander Kreuter17, Jörg HW Distler18, Nicolas Hunzelmann16, Bobby P Koeleman19, Alexandre E Voskuyl20, Annemie J Schuerwegh21, Miguel Ángel González-Gay22, Timothy RDJ Radstake23 and Javier Martin1

Author affiliations

1 Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Avda. del Conocimiento s/n. 18010, Granada, SpainArmilla (Granada), Spain

2 Department of Internal Medicine, Hospital Valle de Hebron, Passeig de la Vall d'Hebron 119 08035 Barcelona, Spain

3 Department of Rheumatology, Radboud University Nijmegen Medical Centre, Comeniuslaan 4 6525 HP Nijmegen, The Netherlands

4 Department of Rheumatology, Hospital 12 de Octubre, Avda. de Córdoba s/n 28041, Madrid, Spain

5 Department of Internal Medicine, Hospital Carlos Haya, Avda Carlos Haya s/n 29010 Málaga, Spain

6 Department of Rheumatology, Hospital Virgen de la Victoria, Campus de Teatinos s/n 29010 Málaga, Spain

7 Department of Rheumatology, Hospital Universitario de Canarias, Ctra. Cuesta-Taco, s/n 38320, La Cuesta, San Cristóbal de La Laguna, Tenerife, Canarias, Spain

8 Department of Internal Medicine, Hospital Central de Asturias, Celestino Villamil, s/n 33006 Oviedo, Spain

9 Department of Autoimmune Diseases, Hospital Clinic, Carrer de Villarroel, 170 08036 Barcelona, Spain

10 See Acknowledgements

11 Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Via Francesco Sforza, 35 20122 and University of Milan, Via Festa del Perdono, 7 20122, Milan, Italy

12 Rheumatology Unit and Chair, Spedali Civili, Università degli Studi, Piazzale Spedali Civili, 1 25123 Brescia, Italy

13 Department of Medicine, Policlinico GB Rossi, Università degli studi di Verona, Via dell'Artigliere, 8 37129 Verona, Italy

14 Department of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany

15 Clinic for Immunology and Rheumatology Medical School, Carl-Neuberg-Str, 1 30625, Hannover, Germany

16 Department of Dermatology, University of Cologne, Kerpener Str 62, 50924 Köln, Germany

17 Department of Dermatology, Allergology, and Venereology, Ruhr University of Bochum, Stiepeler Straße 129 44801 Bochum, Germany

18 Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Schillerstraße 1 91054, Erlangen, Germany

19 Section Complex Genetics, Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg Stratenum 3508 AB, Utrecht, The Netherlands

20 Department of Rheumatology, VU University Medical Center, De Boelelaan 1117 1081 HZ Amsterdam, The Netherlands

21 Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2 2300 RC, Leiden, The Netherlands

22 Department of Rheumatology, Hospital Universitario Marques de Valdecilla, IFIMAV, Avda. Valdecilla, 25, 39008 Santander, Spain

23 Department of Rheumatology and Clinical Immunology, University Utrecht Medical Center, Universiteitsweg 100 Stratenum 3508 AB, Utrecht, The Netherlands

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Citation and License

Arthritis Research & Therapy 2012, 14:R154  doi:10.1186/ar3890

Published: 25 June 2012



The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc).


In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes.


No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis.


Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc.