ABSTRACT 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 Treg marker, 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

for rs2104286 (_P_FDR=2.07 × 10−4, odds ratio=1.30 (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. Access through your institution Buy or subscribe This is a

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LACK OF ASSOCIATION OF THE PLD4 SNP RS2841277 WITH SYSTEMIC SCLEROSIS IN A EUROPEAN AMERICAN POPULATION Article Open access 28 December 2024 SYSTEMIC LUPUS ERYTHEMATOSUS GENETICS: INSIGHTS

INTO PATHOGENESIS AND IMPLICATIONS FOR THERAPY Article 04 September 2024 A SYSTEMATIC REVIEW AND META-ANALYSIS OF HLA CLASS II ASSOCIATIONS IN PATIENTS WITH IGG4 AUTOIMMUNITY Article Open

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visualization of LD and haplotype maps. _Bioinformatics_ 2005; 21: 263–265. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank Sofía Vargas, Sonia García and

Gema Robledo for their excellent technical assistance, and all the patients and healthy controls for kindly accepting their essential collaboration. Banco Nacional de ADN (University of

Salamanca, Spain) and The Norwegian 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. AUTHOR INFORMATION Author notes * J-E Martin, F D Carmona, J C A Broen, C P Simeón, M C Vonk, P Carreira, R

Ríos-Fernández, G Espinosa, E Vicente-Rabaneda, C Tolosa, F J García-Hernández, I Castellví, V Fonollosa, M A González-Gay, L Sáez-Comet, R García Portales, P García de la Peña, M

Fernández-Castro, B Díaz, L Martínez-Estupiñán, M Coenen, A E Voskuyl, A J Schuerwegh, M Vanthuyne, F Houssiau, V Smith, F de Keyser, E De Langhe, G Riemekasten, T Witte, N Hunzelmann, A

Kreuter, Ø Palm, M M Chee, J M van Laar, C Denton, A Herrick, J Worthington, B P C Koeleman, T R D J Radstake, C Fonseca and J Martín: See supplementary note 7. * J-E Martin and F D Carmona:

These authors contributed equally to this work. * T R D J Radstake, C Fonseca and J Martín: These authors share senior authorship. AUTHORS AND AFFILIATIONS * Instituto de Parasitología y

Biomedicina López-Neyra, CSIC, Granada, Spain J-E Martin, F D Carmona & J Martín * Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands J C A

Broen, M C Vonk & T R D J Radstake * Department of Internal Medicine, Hospital Valle de Hebron, Barcelona, Spain C P Simeón & V Fonollosa * Department of Rheumatology, Hospital 12

de Octubre, Madrid, Spain P Carreira * Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain R Ríos-Fernández * Department of Autoimmune Diseases, Hospital Clinic,

Barcelona, Spain G Espinosa * Department of Rheumatology, Hospital de la Princesa, Madrid, Spain E Vicente-Rabaneda * Department of Internal Medicine, Hospital Parc Tauli, Sabadell, Spain C

Tolosa * Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain F J García-Hernández * Department of Rheumatology, Hospital de Sant Pau, Barcelona, Spain I Castellví *

Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain M A González-Gay * Department of Internal Medicine, Hospital Universitario Miguel Servet,

Zaragoza, Spain L Sáez-Comet * Department of Rheumatology, Hospital Virgen de la Victoria, Málaga, Spain R García Portales * Department of Rheumatology, Hospital Universitario Madrid Norte

Sanchinarro, Madrid, Spain P García de la Peña * Department of Rheumatology, Hospital Puerta de Hierro, Madrid, Spain M Fernández-Castro * Department of Internal Medicine, Hospital Central

de Asturias, Oviedo, Spain B Díaz * Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain L Martínez-Estupiñán * Department of Human Genetics, Radboud

University Nijmegen Medical Centre, Nijmegen, The Netherlands M Coenen * Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands A E Voskuyl * Department of

Rheumatology, Leiden University Medical Center, Leiden, The Netherlands A J Schuerwegh * Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium M Vanthuyne 

& F Houssiau * Department of Rheumatology, University of Ghent, Ghent, Belgium V Smith & F de Keyser * University of Leuven (KULeuven), Leuven, Belgium E De Langhe * Department of

Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany G Riemekasten * Hannover Medical School, Hannover, Germany T Witte * Department of Dermatology, University

of Cologne, Cologne, Germany N Hunzelmann * Department of Dermatology, Ruhr University of Bochum, Bochum, Germany A Kreuter * Department of Rheumatology, Rikshospitalet, Oslo University

Hospital, Oslo, Norway Ø Palm * Centre for Rheumatic Diseases, Glasgow Royal Infirmary Glasgow, Glasgow, UK M M Chee * Institute of Cellular Medicine, Newcastle University, Newcastle, UK J M

van Laar * Centre for Rheumatology, Royal Free and University College Medical School, London, UK C Denton & C Fonseca * Arthritis Research UK Epidemiology Unit, The University of

Manchester, Manchester Academic Health Science Centre, Manchester, UK A Herrick & J Worthington * Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The

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DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on Genes and Immunity website

SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Martin, JE., Carmona, F., Broen, J. _et al._ The

autoimmune disease-associated _IL2RA_ locus is involved in the clinical manifestations of systemic sclerosis. _Genes Immun_ 13, 191–196 (2012). https://doi.org/10.1038/gene.2011.72 Download

citation * Received: 17 March 2011 * Revised: 11 August 2011 * Accepted: 19 September 2011 * Published: 20 October 2011 * Issue Date: February 2012 * DOI:

https://doi.org/10.1038/gene.2011.72 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * systemic sclerosis * anti-centromere auto-antibody *

IL2RA * rs11594656 * rs2104286 * rs12722495