Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

Lina-Marcela Diaz-Gallo; Carmen P. Simeon; Jasper C. Broen; Norberto Ortego-Centeno; Lorenzo Beretta; Madelon C. Vonk; Patricia E. Carreira; Sofia Vargas; Jose Andres Roman-Ivorra; Miguel A. Gonzalez-Gay; Carlos Tolosa; Francisco Javier Lopez-Longo; Gerard Espinosa; Esther F. Vicente; Roger Hesselstrand; Gabriela Riemekasten; Torsten Witte; Joerg H. W. Distler; Alexandre E. Voskuyl; Annemie J. Schuerwegh; Paul G. Shiels; Annika Nordin; Leonid Padyukov; Anna-Maria Hoffmann-Vold; Raffaella Scorza; Claudio Lunardi; Paolo Airo; Jacob M. van Laar; Nicolas Hunzelmann; Birgit S. Gathof; Alexander Kreuter; Ariane Herrick; Jane Worthington; Christopher P. Denton; Xiaodong Zhou; Frank C. Arnett; Carmen Fonseca; Bobby P. C. Koeleman; Shervin Assasi; Timothy R. D. J. Radstake; Maureen D. Mayes; Javier Martin

doi:10.1136/annrheumdis-2012-202357

Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

Lina-Marcela Diaz-Gallo^*, Carmen P. Simeon, Jasper C. Broen, Norberto Ortego-Centeno, Lorenzo Beretta, Madelon C. Vonk, Patricia E. Carreira, Sofia Vargas, Jose Andres Roman-Ivorra, Miguel A. Gonzalez-Gay, Carlos Tolosa, Francisco Javier Lopez-Longo, Gerard Espinosa, Esther F. Vicente, Roger Hesselstrand, Gabriela Riemekasten, Torsten Witte, Joerg H. W. Distler, Alexandre E. Voskuyl, Annemie J. SchuerweghPaul G. Shiels, Annika Nordin, Leonid Padyukov, Anna-Maria Hoffmann-Vold, Raffaella Scorza, Claudio Lunardi, Paolo Airo, Jacob M. van Laar, Nicolas Hunzelmann, Birgit S. Gathof, Alexander Kreuter, Ariane Herrick, Jane Worthington, Christopher P. Denton, Xiaodong Zhou, Frank C. Arnett, Carmen Fonseca, Bobby P. C. Koeleman, Shervin Assasi, Timothy R. D. J. Radstake, Maureen D. Mayes, Javier Martin,

^*Corresponding author for this work

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

Abstract

Objective The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc).

Patients and methods The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays.

Results We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (p(c)=6.6E-4 and p(c)=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (p(c)=1.7E-03 and p(c)=8E-4, respectively).

Conclusions These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.

Original language	English
Pages (from-to)	1233-1238
Number of pages	6
Journal	Annals of the Rheumatic Diseases
Volume	72
Issue number	7
DOIs	https://doi.org/10.1136/annrheumdis-2012-202357
Publication status	Published - 2013

Keywords

GENOME-WIDE ASSOCIATION
RHEUMATOID-ARTHRITIS
AUTOIMMUNE-DISEASES
LUPUS-ERYTHEMATOSUS
IL2-IL21 REGION
LOCUS
CONFIRMATION
PATHOGENESIS
RS6822844
IL2/IL21

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http://www.ncbi.nlm.nih.gov/pubmed/?term=23172754

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Diaz-Gallo, L.-M., Simeon, C. P., Broen, J. C., Ortego-Centeno, N., Beretta, L., Vonk, M. C., Carreira, P. E., Vargas, S., Andres Roman-Ivorra, J., Gonzalez-Gay, M. A., Tolosa, C., Javier Lopez-Longo, F., Espinosa, G., Vicente, E. F., Hesselstrand, R., Riemekasten, G., Witte, T., Distler, J. H. W., Voskuyl, A. E. (2013). Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility. Annals of the Rheumatic Diseases, 72(7), 1233-1238. https://doi.org/10.1136/annrheumdis-2012-202357

@article{1166ebe155df446bbbf14985b85ce845,

title = "Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility",

abstract = "Objective The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc).Patients and methods The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays.Results We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (p(c)=6.6E-4 and p(c)=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (p(c)=1.7E-03 and p(c)=8E-4, respectively).Conclusions These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.",

keywords = "GENOME-WIDE ASSOCIATION, RHEUMATOID-ARTHRITIS, AUTOIMMUNE-DISEASES, LUPUS-ERYTHEMATOSUS, IL2-IL21 REGION, LOCUS, CONFIRMATION, PATHOGENESIS, RS6822844, IL2/IL21",

author = "Lina-Marcela Diaz-Gallo and Simeon, {Carmen P.} and Broen, {Jasper C.} and Norberto Ortego-Centeno and Lorenzo Beretta and Vonk, {Madelon C.} and Carreira, {Patricia E.} and Sofia Vargas and {Andres Roman-Ivorra}, Jose and Gonzalez-Gay, {Miguel A.} and Carlos Tolosa and {Javier Lopez-Longo}, Francisco and Gerard Espinosa and Vicente, {Esther F.} and Roger Hesselstrand and Gabriela Riemekasten and Torsten Witte and Distler, {Joerg H. W.} and Voskuyl, {Alexandre E.} and Schuerwegh, {Annemie J.} and Shiels, {Paul G.} and Annika Nordin and Leonid Padyukov and Anna-Maria Hoffmann-Vold and Raffaella Scorza and Claudio Lunardi and Paolo Airo and {van Laar}, {Jacob M.} and Nicolas Hunzelmann and Gathof, {Birgit S.} and Alexander Kreuter and Ariane Herrick and Jane Worthington and Denton, {Christopher P.} and Xiaodong Zhou and Arnett, {Frank C.} and Carmen Fonseca and Koeleman, {Bobby P. C.} and Shervin Assasi and Radstake, {Timothy R. D. J.} and Mayes, {Maureen D.} and Javier Martin",

year = "2013",

doi = "10.1136/annrheumdis-2012-202357",

language = "English",

volume = "72",

pages = "1233--1238",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "Elsevier",

number = "7",

}

Diaz-Gallo, L-M, Simeon, CP, Broen, JC, Ortego-Centeno, N, Beretta, L, Vonk, MC, Carreira, PE, Vargas, S, Andres Roman-Ivorra, J, Gonzalez-Gay, MA, Tolosa, C, Javier Lopez-Longo, F, Espinosa, G, Vicente, EF, Hesselstrand, R, Riemekasten, G, Witte, T, Distler, JHW, Voskuyl, AE, Schuerwegh, AJ, Shiels, PG, Nordin, A, Padyukov, L, Hoffmann-Vold, A-M, Scorza, R, Lunardi, C, Airo, P, van Laar, JM, Hunzelmann, N, Gathof, BS, Kreuter, A, Herrick, A, Worthington, J, Denton, CP, Zhou, X, Arnett, FC, Fonseca, C, Koeleman, BPC, Assasi, S, Radstake, TRDJ, Mayes, MD, Martin, J 2013, 'Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility', Annals of the Rheumatic Diseases, vol. 72, no. 7, pp. 1233-1238. https://doi.org/10.1136/annrheumdis-2012-202357

TY - JOUR

T1 - Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

AU - Diaz-Gallo, Lina-Marcela

AU - Simeon, Carmen P.

AU - Broen, Jasper C.

AU - Ortego-Centeno, Norberto

AU - Beretta, Lorenzo

AU - Vonk, Madelon C.

AU - Carreira, Patricia E.

AU - Vargas, Sofia

AU - Andres Roman-Ivorra, Jose

AU - Gonzalez-Gay, Miguel A.

AU - Tolosa, Carlos

AU - Javier Lopez-Longo, Francisco

AU - Espinosa, Gerard

AU - Vicente, Esther F.

AU - Hesselstrand, Roger

AU - Riemekasten, Gabriela

AU - Witte, Torsten

AU - Distler, Joerg H. W.

AU - Voskuyl, Alexandre E.

AU - Schuerwegh, Annemie J.

AU - Shiels, Paul G.

AU - Nordin, Annika

AU - Padyukov, Leonid

AU - Hoffmann-Vold, Anna-Maria

AU - Scorza, Raffaella

AU - Lunardi, Claudio

AU - Airo, Paolo

AU - van Laar, Jacob M.

AU - Hunzelmann, Nicolas

AU - Gathof, Birgit S.

AU - Kreuter, Alexander

AU - Herrick, Ariane

AU - Worthington, Jane

AU - Denton, Christopher P.

AU - Zhou, Xiaodong

AU - Arnett, Frank C.

AU - Fonseca, Carmen

AU - Koeleman, Bobby P. C.

AU - Assasi, Shervin

AU - Radstake, Timothy R. D. J.

AU - Mayes, Maureen D.

AU - Martin, Javier

PY - 2013

Y1 - 2013

N2 - Objective The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc).Patients and methods The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays.Results We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (p(c)=6.6E-4 and p(c)=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (p(c)=1.7E-03 and p(c)=8E-4, respectively).Conclusions These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.

AB - Objective The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc).Patients and methods The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays.Results We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (p(c)=6.6E-4 and p(c)=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (p(c)=1.7E-03 and p(c)=8E-4, respectively).Conclusions These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.

KW - GENOME-WIDE ASSOCIATION

KW - RHEUMATOID-ARTHRITIS

KW - AUTOIMMUNE-DISEASES

KW - LUPUS-ERYTHEMATOSUS

KW - IL2-IL21 REGION

KW - LOCUS

KW - CONFIRMATION

KW - PATHOGENESIS

KW - RS6822844

KW - IL2/IL21

U2 - 10.1136/annrheumdis-2012-202357

DO - 10.1136/annrheumdis-2012-202357

M3 - Article

C2 - 23172754

SN - 0003-4967

VL - 72

SP - 1233

EP - 1238

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 7

ER -

Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

Abstract

Keywords

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