Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis.

Research output: Contribution to journalArticle


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.


  • 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 Garcia Sanchez
  • María Victoria Egurbide
  • Vicente Fonollosa
  • Paloma García de la Peña
  • Francisco J López-Longo
  • Miguel A González-Gay
  • Gabriela Riemekasten
  • Torsten Witte
  • Alexandre E Voskuyl
  • Annemie J Schuerwegh
  • Rajan Madhok
  • Carmen Fonseca
  • Christopher Denton
  • Annika Nordin
  • Oyvind 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
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity
Original languageEnglish
JournalJournal of Rheumatology
Early online date2012 Oct 1
Publication statusPublished - 2012
Publication categoryResearch