The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis

被引：0
作者：
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
J Martín
机构：
[1] Instituto de Parasitología y Biomedicina López-Neyra,Department of Rheumatology
[2] CSIC,Department of Internal Medicine
[3] Radboud University Nijmegen Medical Centre,Department of Rheumatology
[4] Hospital Valle de Hebron,Department of Internal Medicine
[5] Hospital 12 de Octubre,Department of Autoimmune Diseases
[6] Hospital Clínico San Cecilio,Department of Rheumatology
[7] Hospital Clinic,Department of Internal Medicine
[8] Hospital de la Princesa,Department of Internal Medicine
[9] Hospital Parc Tauli,Department of Rheumatology
[10] Hospital Virgen del Rocío,Department of Rheumatology
[11] Hospital de Sant Pau,Department of Internal Medicine
[12] Hospital Universitario Marqués de Valdecilla,Department of Rheumatology
[13] IFIMAV,Department of Rheumatology
[14] Hospital Universitario Miguel Servet,Department of Rheumatology
[15] Hospital Virgen de la Victoria,Department of Internal Medicine
[16] Hospital Universitario Madrid Norte Sanchinarro,Department of Rheumatology
[17] Hospital Puerta de Hierro,Department of Human Genetics
[18] Hospital Central de Asturias,Department of Rheumatology
[19] Hospital General Universitario Gregorio Marañón,Department of Rheumatology
[20] Radboud University Nijmegen Medical Centre,Department of Rheumatology
[21] VU University Medical Center,Department of Rheumatology and Clinical Immunology
[22] Leiden University Medical Center,Department of Dermatology
[23] Cliniques Universitaires Saint-Luc,Department of Dermatology
[24] Université catholique de Louvain,Department of Rheumatology
[25] University of Ghent,Department of Medical Genetics
[26] University of Leuven (KULeuven),undefined
[27] Charité University Hospital,undefined
[28] Hannover Medical School,undefined
[29] University of Cologne,undefined
[30] Ruhr University of Bochum,undefined
[31] Rikshospitalet,undefined
[32] Oslo University Hospital,undefined
[33] Centre for Rheumatic Diseases,undefined
[34] Glasgow Royal Infirmary Glasgow,undefined
[35] Institute of Cellular Medicine,undefined
[36] Newcastle University,undefined
[37] Centre for Rheumatology,undefined
[38] Royal Free and University College Medical School,undefined
[39] Arthritis Research UK Epidemiology Unit,undefined
[40] The University of Manchester,undefined
[41] Manchester Academic Health Science Centre,undefined
[42] University Medical Center Utrecht,undefined
来源：
Genes & Immunity | 2012年 / 13卷
关键词：
systemic sclerosis; anti-centromere auto-antibody; IL2RA; rs11594656; rs2104286; rs12722495;
D O I：
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学科分类号：
摘要：
Regulatory T cells (Tregs) 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 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 (PFDR=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.
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页码：191 / 196
页数：5
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