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

被引：18

作者：

Martin, J-E ^{[1
]}

Carmona, F. D. ^{[1
]}

Broen, J. C. A. ^{[2
]}

Simeon, C. P. ^{[3
]}

Vonk, M. C. ^{[2
]}

Carreira, P. ^{[4
]}

Rios-Fernandez, R. ^{[5
]}

Espinosa, G. ^{[6
]}

Vicente-Rabaneda, E. ^{[7
]}

Tolosa, C. ^{[8
]}

Garcia-Hernandez, F. J. ^{[9
]}

Castellvi, I. ^{[10
]}

Fonollosa, V. ^{[3
]}

Gonzalez-Gay, M. A. ^{[11
]}

Saez-Comet, L. ^{[12
]}

Garcia Portales, R. ^{[13
]}

Garcia de la Pena, P. ^{[14
]}

Fernandez-Castro, M. ^{[15
]}

Diaz, B. ^{[16
]}

Martinez-Estupinan, L. ^{[17
]}

Coenen, M. ^{[18
]}

Voskuyl, A. E. ^{[19
]}

Schuerwegh, A. J. ^{[20
]}

Vanthuyne, M. ^{[21
]}

Houssiau, F. ^{[21
]}

Smith, V. ^{[22
]}

de Keyser, F. ^{[22
]}

De Langhe, E. ^{[23
]}

Riemekasten, G. ^{[24
]}

Witte, T. ^{[25
]}

Hunzelmann, N. ^{[26
]}

Kreuter, A. ^{[27
]}

Palm, O. ^{[28
]}

Chee, M. M. ^{[29
]}

van Laar, J. M. ^{[30
]}

Denton, C. ^{[31
]}

Herrick, A. ^{[32
]}

Worthington, J. ^{[32
]}

Koeleman, B. P. C. ^{[33
]}

Radstake, T. R. D. J. ^{[2
]}

Fonseca, C. ^{[31
]}

Martin, J. ^{[1
]}

机构：

[1] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain

[2] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands

[3] Hosp Valle de Hebron, Dept Internal Med, Barcelona, Spain

[4] Hosp 12 Octubre, Dept Rheumatol, E-28041 Madrid, Spain

[5] Hosp Clin San Cecilio, Dept Internal Med, Granada, Spain

[6] Hosp Clin Barcelona, Dept Autoimmune Dis, Barcelona, Spain

[7] Hosp Princesa, Dept Rheumatol, Madrid, Spain

[8] Hosp Parc Tauli, Dept Internal Med, Sabadell, Spain

[9] Hosp Virgen del Rocio, Dept Internal Med, Seville, Spain

[10] Hosp Santa Creu & Sant Pau, Dept Rheumatol, Barcelona, Spain

[11] Hosp Univ Marques de Valdecilla, IFIMAV, Dept Rheumatol, Santander, Spain

[12] Hosp Univ Miguel Servet, Dept Internal Med, Zaragoza, Spain

[13] Hosp Virgen de la Victoria, Dept Rheumatol, Malaga, Spain

[14] Hosp Univ Madrid Norte Sanchinarro, Dept Rheumatol, Madrid, Spain

[15] Hosp Puerta de Hierro, Dept Rheumatol, Madrid, Spain

[16] Hosp Cent Asturias, Dept Internal Med, Oviedo, Spain

[17] Hosp Gen Univ Gregorio Maranon, Dept Rheumatol, Madrid, Spain

[18] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands

[19] Vrije Univ Amsterdam Med Ctr, Dept Rheumatol, Amsterdam, Netherlands

[20] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands

[21] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium

[22] Univ Ghent, Dept Rheumatol, B-9000 Ghent, Belgium

[23] Univ Louvain, KULeuven, Louvain, Belgium

[24] Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany

[25] Hannover Med Sch, D-3000 Hannover, Germany

[26] Univ Cologne, Dept Dermatol, Cologne, Germany

[27] Ruhr Univ Bochum, Dept Dermatol, Bochum, Germany

[28] Oslo Univ Hosp, Rikshosp, Dept Rheumatol, Oslo, Norway

[29] Glasgow Royal Infirm, Ctr Rheumat Dis, Glasgow G4 0SF, Lanark, Scotland

[30] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[31] Royal Free & Univ Coll Med Sch, Ctr Rheumatol, London WC1E 6BT, England

[32] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England

[33] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

来源：

GENES AND IMMUNITY | 2012年 / 13卷 / 02期

关键词：

systemic sclerosis; anti-centromere auto-antibody; IL2RA; rs11594656; rs2104286; rs12722495; REGULATORY T-CELLS; INTERLEUKIN-2-RECEPTOR; CLASSIFICATION; PATHOGENESIS;

D O I：

10.1038/gene.2011.72

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 alpha (IL2RA) is an important T-reg 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 (P-FDR 2.07 x 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. Genes and Immunity (2012) 13, 191-196; doi:10.1038/gene.2011.72; published online 20 October 2011

引用

页码：191 / 196

页数：6

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