title: Influence of the IL6 gene in susceptibility to systemic sclerosis.
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).
  
  
  CONCLUSIONS
  Our results suggest that the IL6 gene may influence the development of SSc and its progression.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra,IPBLN-CSIC, Granada, The Netherlands. mccenit@ipb.csic.es
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Cénit
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Simeón
authors.forename: Madelon C
authors.initials: MC
authors.lastname: Vonk
authors.forename: Jose L
authors.initials: JL
authors.lastname: Callejas-Rubio
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Patricia
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authors.lastname: Carreira
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Narvaez
authors.forename: Carlos
authors.initials: C
authors.lastname: Tolosa
authors.forename: José A
authors.initials: JA
authors.lastname: Román-Ivorra
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Gómez-García
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: García-Hernández
authors.forename: María
authors.initials: M
authors.lastname: Gallego
authors.forename: Rosa
authors.initials: R
authors.lastname: García-Portales
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Egurbide
authors.forename: Vicente
authors.initials: V
authors.lastname: Fonollosa
authors.forename: Paloma
authors.initials: P
authors.lastname: García de la Peña
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Longo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Roger
authors.initials: R
authors.lastname: Hesselstrand
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: Annemie J
authors.initials: AJ
authors.lastname: Schuerwegh
authors.forename: Rajan
authors.initials: R
authors.lastname: Madhok
authors.forename: Carmen
authors.initials: C
authors.lastname: Fonseca
authors.forename: Christopher
authors.initials: C
authors.lastname: Denton
authors.forename: Annika
authors.initials: A
authors.lastname: Nordin
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Palm
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hunzelmann
authors.forename: Jörg H W
authors.initials: JH
authors.lastname: Distler
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
authors.forename: Ariane
authors.initials: A
authors.lastname: Herrick
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Bobby P
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000208:ethnology / Q000235:genetics
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6