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, José Andrés Román-Ivorra, Miguel A. González-Gay, Carlos Tolosa, Francisco Javier López-Longo, Gerard Espinosa, Esther F. Vicente, Roger Hesselstrand, Gabriela Riemekasten, Torsten Witte, Jörg 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 Martiń, Jose Luis Callejas, Raquel Ríos, Nuria Navarrete, Rosa García Portales, María Teresa Camps, Antonio Fernández-Nebro, María F. González-Escribano, Julio Sánchez-Román, Francisco J. García-Hernández, Ma Jesús Castillo, Ma Ángeles Aguirre, Inmaculada Gómez-Gracia, Benjamín Fernández-Gutiérrez, Luis Rodríguez-Rodríguez, José Luis Andreu, Paloma García De La Peña, Lina Martínez, María Ángeles Robles, Natividad Oreiro, Vicente Fonollosa, Anna Pros, Mónica Rodríguez Carballeira, Francisco Javier Narváez, Bernardino Díaz, Luis Trapiella, María Gallego, María Del Carmen Freire, Inés Vaqueiro, María Victoria Egurbide, Luis Sáez-Comet, Federico Díaz, Vanesa Hernández, Emma Beltrán

Research output: Contribution to journalArticle

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 pc=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 (pc=1.7E-03 and pc=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 languageEnglish
Pages (from-to)1233-1238
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume72
Issue number7
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Systemic Scleroderma
Genetic Predisposition to Disease
Interleukin-2
Association reactions
Polymorphism
Autoimmune Diseases
Immune system
Chromosomes
Regression analysis
Assays
Nucleotides
Genes
Norway
Skin Diseases
Sweden
Netherlands
Spain
Italy
Single Nucleotide Polymorphism
Germany

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Diaz-Gallo, L. M., Simeon, C. P., Broen, J. C., Ortego-Centeno, N., Beretta, L., Vonk, M. C., ... Beltrán, 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

Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility. / Diaz-Gallo, Lina Marcela; Simeon, Carmen P.; Broen, Jasper C.; Ortego-Centeno, Norberto; Beretta, Lorenzo; Vonk, Madelon C.; Carreira, Patricia E.; Vargas, Sofia; Román-Ivorra, José Andrés; González-Gay, Miguel A.; Tolosa, Carlos; López-Longo, Francisco Javier; Espinosa, Gerard; Vicente, Esther F.; Hesselstrand, Roger; Riemekasten, Gabriela; Witte, Torsten; Distler, Jörg H W; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Shiels, Paul G.; Nordin, Annika; Padyukov, Leonid; Hoffmann-Vold, Anna Maria; Scorza, Raffaella; Lunardi, Claudio; Airo, Paolo; Van Laar, Jacob M.; Hunzelmann, Nicolas; Gathof, Birgit S.; Kreuter, Alexander; Herrick, Ariane; Worthington, Jane; Denton, Christopher P.; Zhou, Xiaodong; Arnett, Frank C.; Fonseca, Carmen; Koeleman, Bobby P C; Assasi, Shervin; Radstake, Timothy R D J; Mayes, Maureen D.; Martiń, Javier; Callejas, Jose Luis; Ríos, Raquel; Navarrete, Nuria; Portales, Rosa García; Camps, María Teresa; Fernández-Nebro, Antonio; González-Escribano, María F.; Sánchez-Román, Julio; García-Hernández, Francisco J.; Castillo, Ma Jesús; Aguirre, Ma Ángeles; Gómez-Gracia, Inmaculada; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Andreu, José Luis; De La Peña, Paloma García; Martínez, Lina; Robles, María Ángeles; Oreiro, Natividad; Fonollosa, Vicente; Pros, Anna; Carballeira, Mónica Rodríguez; Narváez, Francisco Javier; Díaz, Bernardino; Trapiella, Luis; Gallego, María; Del Carmen Freire, María; Vaqueiro, Inés; Egurbide, María Victoria; Sáez-Comet, Luis; Díaz, Federico; Hernández, Vanesa; Beltrán, Emma.

In: Annals of the Rheumatic Diseases, Vol. 72, No. 7, 07.2013, p. 1233-1238.

Research output: Contribution to journalArticle

Diaz-Gallo, LM, Simeon, CP, Broen, JC, Ortego-Centeno, N, Beretta, L, Vonk, MC, Carreira, PE, Vargas, S, Román-Ivorra, JA, González-Gay, MA, Tolosa, C, López-Longo, FJ, Espinosa, G, Vicente, EF, Hesselstrand, R, Riemekasten, G, Witte, T, Distler, JHW, Voskuyl, AE, Schuerwegh, AJ, Shiels, PG, Nordin, A, Padyukov, L, Hoffmann-Vold, AM, 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, Martiń, J, Callejas, JL, Ríos, R, Navarrete, N, Portales, RG, Camps, MT, Fernández-Nebro, A, González-Escribano, MF, Sánchez-Román, J, García-Hernández, FJ, Castillo, MJ, Aguirre, MÁ, Gómez-Gracia, I, Fernández-Gutiérrez, B, Rodríguez-Rodríguez, L, Andreu, JL, De La Peña, PG, Martínez, L, Robles, MÁ, Oreiro, N, Fonollosa, V, Pros, A, Carballeira, MR, Narváez, FJ, Díaz, B, Trapiella, L, Gallego, M, Del Carmen Freire, M, Vaqueiro, I, Egurbide, MV, Sáez-Comet, L, Díaz, F, Hernández, V & Beltrán, E 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
Diaz-Gallo, Lina Marcela ; Simeon, Carmen P. ; Broen, Jasper C. ; Ortego-Centeno, Norberto ; Beretta, Lorenzo ; Vonk, Madelon C. ; Carreira, Patricia E. ; Vargas, Sofia ; Román-Ivorra, José Andrés ; González-Gay, Miguel A. ; Tolosa, Carlos ; López-Longo, Francisco Javier ; Espinosa, Gerard ; Vicente, Esther F. ; Hesselstrand, Roger ; Riemekasten, Gabriela ; Witte, Torsten ; Distler, Jörg H W ; Voskuyl, Alexandre E. ; Schuerwegh, Annemie J. ; Shiels, Paul G. ; Nordin, Annika ; Padyukov, Leonid ; Hoffmann-Vold, Anna Maria ; Scorza, Raffaella ; Lunardi, Claudio ; Airo, Paolo ; Van Laar, Jacob M. ; Hunzelmann, Nicolas ; Gathof, Birgit S. ; Kreuter, Alexander ; Herrick, Ariane ; Worthington, Jane ; Denton, Christopher P. ; Zhou, Xiaodong ; Arnett, Frank C. ; Fonseca, Carmen ; Koeleman, Bobby P C ; Assasi, Shervin ; Radstake, Timothy R D J ; Mayes, Maureen D. ; Martiń, Javier ; Callejas, Jose Luis ; Ríos, Raquel ; Navarrete, Nuria ; Portales, Rosa García ; Camps, María Teresa ; Fernández-Nebro, Antonio ; González-Escribano, María F. ; Sánchez-Román, Julio ; García-Hernández, Francisco J. ; Castillo, Ma Jesús ; Aguirre, Ma Ángeles ; Gómez-Gracia, Inmaculada ; Fernández-Gutiérrez, Benjamín ; Rodríguez-Rodríguez, Luis ; Andreu, José Luis ; De La Peña, Paloma García ; Martínez, Lina ; Robles, María Ángeles ; Oreiro, Natividad ; Fonollosa, Vicente ; Pros, Anna ; Carballeira, Mónica Rodríguez ; Narváez, Francisco Javier ; Díaz, Bernardino ; Trapiella, Luis ; Gallego, María ; Del Carmen Freire, María ; Vaqueiro, Inés ; Egurbide, María Victoria ; Sáez-Comet, Luis ; Díaz, Federico ; Hernández, Vanesa ; Beltrán, Emma. / Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility. In: Annals of the Rheumatic Diseases. 2013 ; Vol. 72, No. 7. pp. 1233-1238.
@article{f6799a3e87b54ab98b9d9b477d489905,
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 pc=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 (pc=1.7E-03 and pc=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.",
author = "Diaz-Gallo, {Lina Marcela} 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 Rom{\'a}n-Ivorra, {Jos{\'e} Andr{\'e}s} and Gonz{\'a}lez-Gay, {Miguel A.} and Carlos Tolosa and L{\'o}pez-Longo, {Francisco Javier} and Gerard Espinosa and Vicente, {Esther F.} and Roger Hesselstrand and Gabriela Riemekasten and Torsten Witte and Distler, {J{\"o}rg H W} and Voskuyl, {Alexandre E.} and Schuerwegh, {Annemie J.} and Shiels, {Paul G.} and Annika Nordin and Leonid Padyukov and Hoffmann-Vold, {Anna Maria} 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 Martiń and Callejas, {Jose Luis} and Raquel R{\'i}os and Nuria Navarrete and Portales, {Rosa Garc{\'i}a} and Camps, {Mar{\'i}a Teresa} and Antonio Fern{\'a}ndez-Nebro and Gonz{\'a}lez-Escribano, {Mar{\'i}a F.} and Julio S{\'a}nchez-Rom{\'a}n and Garc{\'i}a-Hern{\'a}ndez, {Francisco J.} and Castillo, {Ma Jes{\'u}s} and Aguirre, {Ma {\'A}ngeles} and Inmaculada G{\'o}mez-Gracia and Benjam{\'i}n Fern{\'a}ndez-Guti{\'e}rrez and Luis Rodr{\'i}guez-Rodr{\'i}guez and Andreu, {Jos{\'e} Luis} and {De La Pe{\~n}a}, {Paloma Garc{\'i}a} and Lina Mart{\'i}nez and Robles, {Mar{\'i}a {\'A}ngeles} and Natividad Oreiro and Vicente Fonollosa and Anna Pros and Carballeira, {M{\'o}nica Rodr{\'i}guez} and Narv{\'a}ez, {Francisco Javier} and Bernardino D{\'i}az and Luis Trapiella and Mar{\'i}a Gallego and {Del Carmen Freire}, Mar{\'i}a and In{\'e}s Vaqueiro and Egurbide, {Mar{\'i}a Victoria} and Luis S{\'a}ez-Comet and Federico D{\'i}az and Vanesa Hern{\'a}ndez and Emma Beltr{\'a}n",
year = "2013",
month = "7",
doi = "10.1136/annrheumdis-2012-202357",
language = "English",
volume = "72",
pages = "1233--1238",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "7",

}

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 - Román-Ivorra, José Andrés

AU - González-Gay, Miguel A.

AU - Tolosa, Carlos

AU - López-Longo, Francisco Javier

AU - Espinosa, Gerard

AU - Vicente, Esther F.

AU - Hesselstrand, Roger

AU - Riemekasten, Gabriela

AU - Witte, Torsten

AU - Distler, Jörg 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 - Martiń, Javier

AU - Callejas, Jose Luis

AU - Ríos, Raquel

AU - Navarrete, Nuria

AU - Portales, Rosa García

AU - Camps, María Teresa

AU - Fernández-Nebro, Antonio

AU - González-Escribano, María F.

AU - Sánchez-Román, Julio

AU - García-Hernández, Francisco J.

AU - Castillo, Ma Jesús

AU - Aguirre, Ma Ángeles

AU - Gómez-Gracia, Inmaculada

AU - Fernández-Gutiérrez, Benjamín

AU - Rodríguez-Rodríguez, Luis

AU - Andreu, José Luis

AU - De La Peña, Paloma García

AU - Martínez, Lina

AU - Robles, María Ángeles

AU - Oreiro, Natividad

AU - Fonollosa, Vicente

AU - Pros, Anna

AU - Carballeira, Mónica Rodríguez

AU - Narváez, Francisco Javier

AU - Díaz, Bernardino

AU - Trapiella, Luis

AU - Gallego, María

AU - Del Carmen Freire, María

AU - Vaqueiro, Inés

AU - Egurbide, María Victoria

AU - Sáez-Comet, Luis

AU - Díaz, Federico

AU - Hernández, Vanesa

AU - Beltrán, Emma

PY - 2013/7

Y1 - 2013/7

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 pc=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 (pc=1.7E-03 and pc=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 pc=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 (pc=1.7E-03 and pc=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.

UR - http://www.scopus.com/inward/record.url?scp=84878435061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878435061&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2012-202357

DO - 10.1136/annrheumdis-2012-202357

M3 - Article

C2 - 23172754

AN - SCOPUS:84878435061

VL - 72

SP - 1233

EP - 1238

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 7

ER -