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

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 Pẽa; M. Fernández-Castro; B. Díaz; L. Martínez-Estupĩán; 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; Øyvind 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

doi:10.1038/gene.2011.72

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

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 Pẽa, M. Fernández-Castro, B. Díaz, L. Martínez-EstupĩánM. 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, Øyvind 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

Research output: Contribution to journal › Article › peer-review

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 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. © 2012 Macmillan Publishers Limited All rights reserved.

Original language	English
Pages (from-to)	191-196
Number of pages	5
Journal	Genes and Immunity
Volume	13
Issue number	2
DOIs	https://doi.org/10.1038/gene.2011.72
Publication status	Published - Feb 2012

Keywords

anti-centromere auto-antibody
IL2RA
rs11594656
rs12722495
rs2104286
systemic sclerosis

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10.1038/gene.2011.72

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Martin, J. E., Carmona, F. D., Broen, J. C. A., Simeón, C. P., Vonk, M. C., Carreira, P., Ríos-Fernández, R., Espinosa, G., Vicente-Rabaneda, E., Tolosa, C., García-Hernández, F. J., Castellví, I., Fonollosa, V., González-Gay, M. A., Sáez-Comet, L., Portales, R. G., De La Pẽa, P. G., Fernández-Castro, M., Díaz, B., ... Martín, J. (2012). The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis. Genes and Immunity, 13(2), 191-196. https://doi.org/10.1038/gene.2011.72

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

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 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. {\textcopyright} 2012 Macmillan Publishers Limited All rights reserved.",

keywords = "anti-centromere auto-antibody, IL2RA, rs11594656, rs12722495, rs2104286, systemic sclerosis",

author = "Martin, {J. E.} and Carmona, {F. D.} and Broen, {J. C A} and Sime{\'o}n, {C. P.} and Vonk, {M. C.} and P. Carreira and R. R{\'i}os-Fern{\'a}ndez and G. Espinosa and E. Vicente-Rabaneda and C. Tolosa and Garc{\'i}a-Hern{\'a}ndez, {F. J.} and I. Castellv{\'i} and V. Fonollosa and Gonz{\'a}lez-Gay, {M. A.} and L. S{\'a}ez-Comet and Portales, {R. Garc{\'i}a} and {De La Pẽa}, {P. Garc{\'i}a} and M. Fern{\'a}ndez-Castro and B. D{\'i}az and L. Mart{\'i}nez-Estupĩ{\'a}n and M. Coenen and Voskuyl, {A. E.} and Schuerwegh, {A. J.} and M. Vanthuyne and F. Houssiau and V. Smith and {De Keyser}, F. and {De Langhe}, E. and G. Riemekasten and T. Witte and N. Hunzelmann and A. Kreuter and {\O}yvind Palm and Chee, {M. M.} and {Van Laar}, {J. M.} and C. Denton and A. Herrick and J. Worthington and Koeleman, {B. P C} and Radstake, {T. R D J} and C. Fonseca and J. Mart{\'i}n",

year = "2012",

month = feb,

doi = "10.1038/gene.2011.72",

language = "English",

volume = "13",

pages = "191--196",

journal = "Genes and Immunity",

issn = "1466-4879",

publisher = "Springer Nature",

number = "2",

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Martin, JE, Carmona, FD, Broen, JCA, Simeón, CP, Vonk, MC, Carreira, P, Ríos-Fernández, R, Espinosa, G, Vicente-Rabaneda, E, Tolosa, C, García-Hernández, FJ, Castellví, I, Fonollosa, V, González-Gay, MA, Sáez-Comet, L, Portales, RG, De La Pẽa, PG, Fernández-Castro, M, Díaz, B, Martínez-Estupĩán, L, Coenen, M, Voskuyl, AE, Schuerwegh, AJ, Vanthuyne, M, Houssiau, F, Smith, V, De Keyser, F, De Langhe, E, Riemekasten, G, Witte, T, Hunzelmann, N, Kreuter, A, Palm, Ø, Chee, MM, Van Laar, JM, Denton, C, Herrick, A , Worthington, J, Koeleman, BPC, Radstake, TRDJ, Fonseca, C & Martín, J 2012, 'The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis', Genes and Immunity, vol. 13, no. 2, pp. 191-196. https://doi.org/10.1038/gene.2011.72

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, Øyvind

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.

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. © 2012 Macmillan Publishers Limited All rights reserved.

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. © 2012 Macmillan Publishers Limited All rights reserved.

KW - anti-centromere auto-antibody

KW - IL2RA

KW - rs11594656

KW - rs12722495

KW - rs2104286

KW - systemic sclerosis

U2 - 10.1038/gene.2011.72

DO - 10.1038/gene.2011.72

M3 - Article

C2 - 22012429

SN - 1466-4879

VL - 13

SP - 191

EP - 196

JO - Genes and Immunity

JF - Genes and Immunity

IS - 2

ER -

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

Abstract

Keywords

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