TY - JOUR
T1 - The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis
AU - Martin, J. E.
AU - Carmona, F. D.
AU - Broen, J. C.A.
AU - Simeón, C. P.
AU - Vonk, M. C.
AU - Carreira, P.
AU - Ríos-Fernández, R.
AU - Espinosa, G.
AU - Vicente-Rabaneda, E.
AU - Tolosa, C.
AU - García-Hernández, F. J.
AU - Castellví, I.
AU - Fonollosa, V.
AU - González-Gay, M. A.
AU - Sáez-Comet, L.
AU - Portales, R. García
AU - De La Pẽa, P. García
AU - Fernández-Castro, M.
AU - Díaz, B.
AU - Martínez-Estupĩán, L.
AU - Coenen, M.
AU - Voskuyl, A. E.
AU - Schuerwegh, A. J.
AU - Vanthuyne, M.
AU - Houssiau, F.
AU - Smith, V.
AU - De Keyser, F.
AU - De Langhe, E.
AU - Riemekasten, G.
AU - Witte, T.
AU - Hunzelmann, N.
AU - Kreuter, A.
AU - Palm,
AU - Chee, M. M.
AU - Van Laar, J. M.
AU - Denton, C.
AU - Herrick, A.
AU - Worthington, J.
AU - Koeleman, B. P.C.
AU - Radstake, T. R.D.J.
AU - Fonseca, C.
AU - Martín, J.
N1 - Funding Information:
Bone Marrow Donor Registry are thanked for supplying part of the control material. We are also thankful to EUSTAR and the German Network of Systemic Sclerosis for the facilitation of this project. This work was supported by the following grants: JM was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 and CTS-180 from Junta de Andalucía, and in part by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain. FDC was supported by Consejo Superior de Investigaciones Científicas (CSIC) through the program JAE-DOC. TRDJR was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). CF is supported by ‘The Raynaud’s and Scleroderma Association’ and ‘The Scleroderma Society’. JM and TRDJR were sponsored by the Orphan Disease Program grant from EULAR. TW was granted by DFG WI 1031/6.1.
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/2
Y1 - 2012/2
N2 - Regulatory T cells (T regs) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T regmarker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P FDR 2.07 × 10 -4,odds ratio1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc.
AB - Regulatory T cells (T regs) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T regmarker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P FDR 2.07 × 10 -4,odds ratio1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc.
UR - http://www.scopus.com/inward/record.url?scp=84857782321&partnerID=8YFLogxK
U2 - 10.1038/gene.2011.72
DO - 10.1038/gene.2011.72
M3 - Journal articles
C2 - 22012429
AN - SCOPUS:84857782321
SN - 1466-4879
VL - 13
SP - 191
EP - 196
JO - Genes and Immunity
JF - Genes and Immunity
IS - 2
ER -