Journal
ARTHRITIS RESEARCH & THERAPY
Volume 14, Issue 2, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/ar3809
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Funding
- GENFER from the Spanish Society of Rheumatology
- Spanish Ministry of Science [SAF2009-11110]
- Junta de Andalucia, Spain [CTS-4977]
- Redes Tematicas de Investigacion Cooperativa Sanitaria Program
- Instituto de Salud Carlos III (ISCIII), Spain [RD08/0075]
- Fondo Europeo de Desarrollo Regional (FEDER)
- VIDI laureate from the Dutch Association of Research (NWO)
- Dutch Arthritis Foundation (National Reumafonds)
- Orphan Disease Program grant from the European League Against Rheumatism (EULAR)
- Dutch Diabetes Research Foundation [2008.40.001]
- Dutch Arthritis Foundation (Reumafonds) [NR 09-1-408]
- DFG WI [1031/6.1]
- Consejeria de Salud, Junta de Andalucia, Spain [PI-0590-2010]
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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 (P-Bonf = 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.
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