Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Association of the Functional CD226 307Ser Variant with Systemic Sclerosis (SSc): Evidence for the Contribution of Co-Stimulation Pathways in the SSc Pathogenesis.

Dieude10,  Philippe, Guedj6,  Mickaël, Truchetet4,  Marie-Elise, Riemekasten3,  Gabriela, Matucci-Cerinic2,  Marco, Melchers1,  Inga, Hachulla8,  Eric

Clinical Research Unit for Rheumatology, University Medical Center, Freiburg, Germany
Université Paris Diderot, Service de Rhumatologie, Hôpital Bichat Claude Bernard, APHP, Paris, France
Université Versailles Saint Quentin Yvelines, Laboratoire de Biochimie Hormonale et Génétique, Hôpital Ambroise Paré, AP-HP, Boulogne, France
Department of Biomedicine, Section of Rheumatology, Florence, Italy
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany
Immunology and Allergy, Geneva University Hospital and School of Medicine, Geneva, Switzerland
Immunology and Allergy, Geneva University Hospital and School of Medicine, Geneva, Switzerland
Laboratoire Statistique et Génome, UMR CNRS-8071/INRA-1152/Université d'Evry Val d'Essonne, France
Rheumatology and Clinical Immunology, Spedali Civili, Brescia, Italy
Université Lille II, Médecine Interne, Lille, France
Université Paris Descartes, Service de Rhumatologie A, Hôpital Cochin, Paris, France

Background:

The non-synonymous polymorphism rs763361 of the CD226 gene, which encodes the DNAX accessory molecule 1, involved in T cell co-stimulation pathways, has recently been identified as a genetic risk factor for autoimmunity.

Objective:

To test for association the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations.

Methods:

CD226 rs763361 was genotyped in 3645 individuals comprising a discovery set (991 SSc patients and 1008 controls) and a replication set (999 SSc patients and 634 controls), all individuals being of European Caucasian origin.

Results:

The CD226 rs763361 T allele was found to be associated with SSc in both discovery and replication samples providing the following results in the combined populations: OR 1.22 95%CI [1.10–1.34], P=5.69×10-5. The CD226 T allele was also associated with various SSc subsets highlighting a potential contribution in disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with diffuse cutaneous subtype, anti-topoisomerase I antibodies positive and SSc-related fibrosing alveolitis subsets: OR 1.86 95%CI [1.42–2.43], P=5.15×10-6, OR 1.82 95%CI [1.38–2.40], P=2.16×10-6 and OR 1.61 95%CI [1.25–2.08], P=2.73×10-4, respectively.

 TT (%)TC (%)CC (%)T (%) P*POR (95% CI)
Discovery set
SSc n = 99122.850.826.448.2T0.023NS1.15 [1.02–1.31]
     TT0.016NS1.37 [1.06–1.77]
     TC0.49NS1.07 [0.87–1.32]
Controls n = 100818.452.329.344.6    
Replication set
SSc n = 99627.951.021.153.4T0.00180.0181.25 [1.09–1.44]
     TT0.00170.0171.56 [1.15–2.06]
     TC0.00250.0251.45 [1.14–1.85]
Controls n = 65024.147.428.547.4    
Combined populations
SSc n = 198725.450.923.750.8T2.67 × 1051.22 [1.11–1.34]
     TT2.47 × 1031.49 [1.24–1.80]
     TC0.00911.23 [1.05–1.44]
Controls n = 165820.750.428.945.9    
*By chi-square test or Fisher's exact test.
P-value < 0.05 adjusted after Bonferroni's corrections for multiple comparison. NS: not statistically significant.

Conclusions:

Our results establish CD226 as a new SSc genetic susceptibility factor.

To cite this abstract, please use the following information:
Dieude, Philippe, Guedj, Mickaël, Truchetet, Marie-Elise, Riemekasten, Gabriela, Matucci-Cerinic, Marco, Melchers, Inga, et al; Association of the Functional CD226 307Ser Variant with Systemic Sclerosis (SSc): Evidence for the Contribution of Co-Stimulation Pathways in the SSc Pathogenesis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1987
DOI: 10.1002/art.29752

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