Research article
A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis
- † Equal contributors
1 Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Avenida del Conocimiento s/n, Granada, 18100, Spain
2 Servicio de Medicina Interna, Hospital Valle de Hebron, Passeig de la Vall d'Hebron, 119-129, Barcelona, 08035, Spain
3 IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena and University of Milan, Allergy, Clinical Immunology and Rheumatology, Via Francesco Sforza 28, Milan, 20122, Italy
4 Department of Rheumatology, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 10, Nijmegen, 6525 GA, The Netherlands
5 Servicio de Medicina Interna, Hospital Clínico Universitario, Avenida Doctor Olóriz 16, Granada, 18012, Spain
6 Servicio de Enfermedades Autoinmunes, Hospital Clinic, C/Villarroel, 170, Barcelona, 08036, Spain
7 Servicio de Reumatología, Hospital 12 de Octubre, Avenida de Córdoba, s/n, Madrid, 28041, Spain
8 Servicio de Medicina Interna, Hospital Carlos Haya, Avenida Carlos Haya s/n, Málaga, 29010, Spain
9 Servicio de Medicina Interna, Hospital Virgen del Rocío, Avenida Manuel Siurot s/n, Sevilla, 41013, Spain
10 Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, IFIMAV, Avenida Valdecilla 25, Santander, 39008, Spain
11 Servicio de Reumatología, Hospital del Doctor Peset Aleixandre, Avenida Gaspar Aguilar 90, Valencia, 46017, Spain
12 Unidad Trombosis y Vasculitis, Servicio de Medicina Interna, Hospital Xeral-Complexo Hospitalario Universitario de Vigo, Rua Pizarro 22, Vigo, 36204, Spain
13 Servicio de Reumatología, Hospital Universitario de Bellvitge, C/Feixa Llarga s/n, 08907, Barcelona, Spain
14 Servicio de Medicina Interna, Hospital Parc Taulí, Parc del Taulí s/n, Sabadell, 08208, Spain
15 Hannover Medical School, Carl-Neuberg-Straße 1, Hannover, 30625, Germany
16 Ruhr University of Bochum, Universitätsstraße 150, Bochum, 44801, Germany
17 Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands
18 Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, 0027, Norway
19 Department of Rheumatology, Lund University, Paradisgatan 2, Lund, SE-221 00, Sweden
20 Department of Medicine, Università degli Studi di Verona, Via dell'Artigliere, 19, Verona 37129, Italy
21 Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, Newcastle, NE2 4HH, UK
22 Centre for Rheumatic Diseases, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK
23 Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester, M13 9PT, UK
24 Section Complex Genetics, Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands
25 Centre for Rheumatology, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 PF, UK
26 Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands
Arthritis Research & Therapy 2012, 14:R85 doi:10.1186/ar3809
Published: 24 April 2012Abstract
Introduction
CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population.
Methods
A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays.
Results
Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)).
Conclusion
Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis.
