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Research ArticleArticle

Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

MARIA CARMEN CÉNIT, CARMEN P. SIMEÓN, MADELON C. VONK, JOSE L. CALLEJAS-RUBIO, GERARD ESPINOSA, PATRICIA CARREIRA, FRANCISCO J. BLANCO, JAVIER NARVAEZ, CARLOS TOLOSA, JOSÉ A. ROMÁN-IVORRA, INMACULADA GÓMEZ-GARCÍA, FRANCISCO J. GARCÍA-HERNÁNDEZ, MARÍA GALLEGO, ROSA GARCÍA-PORTALES, MARÍA VICTORIA EGURBIDE, VICENTE FONOLLOSA, PALOMA GARCÍA de la PEÑA, FRANCISCO J. LÓPEZ-LONGO, MIGUEL A. GONZÁLEZ-GAY, The Spanish Scleroderma Group, ROGER HESSELSTRAND, GABRIELA RIEMEKASTEN, TORSTEN WITTE, ALEXANDRE E. VOSKUYL, ANNEMIE J. SCHUERWEGH, RAJAN MADHOK, CARMEN FONSECA, CHRISTOPHER DENTON, ANNIKA NORDIN, ØYVIND PALM, JACOB M. van LAAR, NICOLAS HUNZELMANN, JÖRG H.W. DISTLER, ALEXANDER KREUTER, ARIANE HERRICK, JANE WORTHINGTON, BOBBY P. KOELEMAN, TIMOTHY R.D.J. RADSTAKE and JAVIER MARTÍN
The Journal of Rheumatology December 2012, 39 (12) 2294-2302; DOI: https://doi.org/10.3899/jrheum.120506
MARIA CARMEN CÉNIT
From the Instituto de Parasitología y Biomedicina López-Neyra,IPBLN-CSIC, Granada; Department of Internal Medicine, Hospital Valle de Hebron, Barcelona, Spain; Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Internal Medicine, Hospital Clínico Universitario, Granada; Department of Internal Medicine, Hospital Clínico de Barcelona, Barcelona; Department of Rheumatology, Hospital 12 de Octubre, Madrid; Complejo Hospitalario Universitario a Coruña, La Coruña; Department of Rheumatology, Hospital de Bellvitge, Barcelona; Department of Internal Medicine, Hospital Parc Tauli, Sabadell; Department of Rheumatology, Hospital La Fe, Valencia; Department of Rheumatology, Hospital Reina Sofía, Córdoba; Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla; Department of Internal Medicine, Hospital Central de Asturias, Oviedo; Department of Rheumatology, Hospital Virgen de la Victoria, Málaga; Department of Internal Medicine, Hospital de Cruces, Barakaldo; Department of Rheumatology, Hospital Madrid Norte Sanchinarro, Madrid; Department of Rheumatology, Hospital General Universitario Gregorio Marañón; Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain; Department of Rheumatology, Lund University, Lund, Sweden; German Rheumatismus Research Centre, Leibniz Institute, Germany; Clinic for Immunology and Rheumatology Medical School, Hannover, Germany; Department of Rheumatology, VU University Medical Center, Amsterdam; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Centre for Rheumatic Disease University of Glasgow, Glasgow; Centre for Rheumatology, Royal Free and University College Medical School, London, UK; Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway; Institute of Cellular Medicine, Newcastle University, Newcastle, UK; Department of Dermatology, University of Cologne, Cologne; Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen; Klinik für Dermatologie, Venerologie und Allergologie, Ruhr University of Bochum, Bochum, Germany; Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Department of Medical Genetics, University Medical Center Utrecht, Utrecht; and Department of Rheumatology and Clinical Immunology, Utrecht Medical Center, Utrecht, The Netherlands.
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  • For correspondence: mccenit@ipb.csic.es
CARMEN P. SIMEÓN
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MADELON C. VONK
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JOSE L. CALLEJAS-RUBIO
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GERARD ESPINOSA
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PATRICIA CARREIRA
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FRANCISCO J. BLANCO
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JAVIER NARVAEZ
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CARLOS TOLOSA
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JOSÉ A. ROMÁN-IVORRA
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INMACULADA GÓMEZ-GARCÍA
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FRANCISCO J. GARCÍA-HERNÁNDEZ
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MARÍA GALLEGO
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ROSA GARCÍA-PORTALES
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MARÍA VICTORIA EGURBIDE
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VICENTE FONOLLOSA
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PALOMA GARCÍA de la PEÑA
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FRANCISCO J. LÓPEZ-LONGO
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MIGUEL A. GONZÁLEZ-GAY
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ROGER HESSELSTRAND
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GABRIELA RIEMEKASTEN
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TORSTEN WITTE
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ALEXANDRE E. VOSKUYL
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ANNEMIE J. SCHUERWEGH
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RAJAN MADHOK
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CARMEN FONSECA
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CHRISTOPHER DENTON
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ANNIKA NORDIN
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ØYVIND PALM
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JACOB M. van LAAR
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NICOLAS HUNZELMANN
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JÖRG H.W. DISTLER
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ALEXANDER KREUTER
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ARIANE HERRICK
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JANE WORTHINGTON
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BOBBY P. KOELEMAN
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TIMOTHY R.D.J. RADSTAKE
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JAVIER MARTÍN
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Abstract

Objective. Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc.

Methods. We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology.

Results. Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04–1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77–0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04–1.23).

Conclusion. Our results suggest that the IL6 gene may influence the development of SSc and its progression.

Key Indexing Terms:
  • SYSTEMIC SCLEROSIS
  • SCLERODERMA
  • IL6 GENE
  • POLYMORPHISMS
  • GENETIC STUDIES

Footnotes

  • J. Martín was supported by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-180 from Junta de Andalucía, RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain, within the VI PN de I+D+i 2008-2011 (FEDER). T.R.D.J. Radstake and J. Martín are sponsored by the Orphan Disease Program grant from European League Against Rheumatism. N. Ortego-Centeno and J. Martín are supported by Consejería de Salud, Junta de Andalucía, PI-0590-2010.

  • Accepted for publication July 4, 2012.
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The Journal of Rheumatology: 39 (12)
The Journal of Rheumatology
Vol. 39, Issue 12
1 Dec 2012
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Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis
MARIA CARMEN CÉNIT, CARMEN P. SIMEÓN, MADELON C. VONK, JOSE L. CALLEJAS-RUBIO, GERARD ESPINOSA, PATRICIA CARREIRA, FRANCISCO J. BLANCO, JAVIER NARVAEZ, CARLOS TOLOSA, JOSÉ A. ROMÁN-IVORRA, INMACULADA GÓMEZ-GARCÍA, FRANCISCO J. GARCÍA-HERNÁNDEZ, MARÍA GALLEGO, ROSA GARCÍA-PORTALES, MARÍA VICTORIA EGURBIDE, VICENTE FONOLLOSA, PALOMA GARCÍA de la PEÑA, FRANCISCO J. LÓPEZ-LONGO, MIGUEL A. GONZÁLEZ-GAY, The Spanish Scleroderma Group, ROGER HESSELSTRAND, GABRIELA RIEMEKASTEN, TORSTEN WITTE, ALEXANDRE E. VOSKUYL, ANNEMIE J. SCHUERWEGH, RAJAN MADHOK, CARMEN FONSECA, CHRISTOPHER DENTON, ANNIKA NORDIN, ØYVIND PALM, JACOB M. van LAAR, NICOLAS HUNZELMANN, JÖRG H.W. DISTLER, ALEXANDER KREUTER, ARIANE HERRICK, JANE WORTHINGTON, BOBBY P. KOELEMAN, TIMOTHY R.D.J. RADSTAKE, JAVIER MARTÍN
The Journal of Rheumatology Dec 2012, 39 (12) 2294-2302; DOI: 10.3899/jrheum.120506

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Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis
MARIA CARMEN CÉNIT, CARMEN P. SIMEÓN, MADELON C. VONK, JOSE L. CALLEJAS-RUBIO, GERARD ESPINOSA, PATRICIA CARREIRA, FRANCISCO J. BLANCO, JAVIER NARVAEZ, CARLOS TOLOSA, JOSÉ A. ROMÁN-IVORRA, INMACULADA GÓMEZ-GARCÍA, FRANCISCO J. GARCÍA-HERNÁNDEZ, MARÍA GALLEGO, ROSA GARCÍA-PORTALES, MARÍA VICTORIA EGURBIDE, VICENTE FONOLLOSA, PALOMA GARCÍA de la PEÑA, FRANCISCO J. LÓPEZ-LONGO, MIGUEL A. GONZÁLEZ-GAY, The Spanish Scleroderma Group, ROGER HESSELSTRAND, GABRIELA RIEMEKASTEN, TORSTEN WITTE, ALEXANDRE E. VOSKUYL, ANNEMIE J. SCHUERWEGH, RAJAN MADHOK, CARMEN FONSECA, CHRISTOPHER DENTON, ANNIKA NORDIN, ØYVIND PALM, JACOB M. van LAAR, NICOLAS HUNZELMANN, JÖRG H.W. DISTLER, ALEXANDER KREUTER, ARIANE HERRICK, JANE WORTHINGTON, BOBBY P. KOELEMAN, TIMOTHY R.D.J. RADSTAKE, JAVIER MARTÍN
The Journal of Rheumatology Dec 2012, 39 (12) 2294-2302; DOI: 10.3899/jrheum.120506
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Keywords

SYSTEMIC SCLEROSIS
SCLERODERMA
IL6 GENE
POLYMORPHISMS
GENETIC STUDIES

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Keywords

  • SYSTEMIC SCLEROSIS
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  • IL6 GENE
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  • GENETIC STUDIES

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