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).
  
  
  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 (pc=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.
authors.affiliation: Cellular Biology and Immunology Department, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain. lina.diaz@ipb.csic.es
authors.forename: Lina-Marcela
authors.initials: LM
authors.lastname: Diaz-Gallo
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Simeon
authors.forename: Jasper C
authors.initials: JC
authors.lastname: Broen
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.forename: Madelon C
authors.initials: MC
authors.lastname: Vonk
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Carreira
authors.forename: Sofia
authors.initials: S
authors.lastname: Vargas
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Román-Ivorra
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Carlos
authors.initials: C
authors.lastname: Tolosa
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: López-Longo
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Esther F
authors.initials: EF
authors.lastname: Vicente
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: Jörg H W
authors.initials: JH
authors.lastname: Distler
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: Annemie J
authors.initials: AJ
authors.lastname: Schuerwegh
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
authors.forename: Annika
authors.initials: A
authors.lastname: Nordin
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Hoffmann-Vold
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Airo
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hunzelmann
authors.forename: Birgit S
authors.initials: BS
authors.lastname: Gathof
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: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
authors.forename: Carmen
authors.initials: C
authors.lastname: Fonseca
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Shervin
authors.initials: S
authors.lastname: Assasi
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D045743:Scleroderma, Diffuse / Q000208:ethnology / Q000235:genetics; D045745:Scleroderma, Limited / Q000208:ethnology / Q000235:genetics; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics; D000098546:Interleukin-21
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21