title: Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression.
abstract: OBJECTIVE
  Polymorphisms in the genes encoding interleukin 4 (IL4), interleukin 13 (IL13), and their corresponding receptors have been associated with multiple immune-mediated diseases. Our aim was to validate these previous observations in patients with systemic sclerosis (SSc) and scrutinize the effect of the polymorphisms on gene expression in various populations of peripheral blood leukocytes.
  
  
  METHODS
  We genotyped a cohort of 2488 patients with SSc and 2246 healthy controls from The Netherlands, Spain, United Kingdom, Italy, Germany, and France. Taqman assays were used to genotype single-nucleotide polymorphisms (SNP) in the following genes: (1) IL4 (-590C>T/rs2243250); (2) IL4 receptor alpha (IL4RA) (Q576R/rs1801275); (3) IL13 (R130Q/rs20541 and -1112C>T/rs1800925); and (4) IL13RA1 (43163G>A/rs6646259). The effect of these polymorphisms on expression of the corresponding genes was assessed using quantitative RT-PCR on RNA derived from peripheral blood B cells, T cells, plasmacytoid dendritic cells, monocytes, and myeloid dendritic cells. We investigated whether these polymorphisms influenced development of pulmonary complications over 15 years in patients with SSc.
  
  
  RESULTS
  None of the investigated polymorphisms was associated with SSc or any SSc clinical subtype. We did not observe any effect on transcript levels in the cell subtypes or on development of pulmonary complications.
  
  
  CONCLUSIONS
  Our data showed that polymorphisms in IL4, IL13, and their receptors do not play a role in SSc and do not influence the expression of their corresponding transcript in peripheral blood cells.
authors: Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands.
authors: Jasper C A
authors: JC
authors: Broen
authors: Phillipe
authors: P
authors: Dieude
authors: Madelon C
authors: MC
authors: Vonk
authors: Lorenzo
authors: L
authors: Beretta
authors: Francisco D
authors: FD
authors: Carmona
authors: Ariane
authors: A
authors: Herrick
authors: Jane
authors: J
authors: Worthington
authors: Nicholas
authors: N
authors: Hunzelmann
authors: Gabriela
authors: G
authors: Riemekasten
authors: Hans
authors: H
authors: Kiener
authors: Rafaella
authors: R
authors: Scorza
authors: Carmen P
authors: CP
authors: Simeon
authors: Vicent
authors: V
authors: Fonollosa
authors: Patricia
authors: P
authors: Carreira
authors: Norberto
authors: N
authors: Ortego-Centeno
authors: Miguel A
authors: MA
authors: Gonzalez-Gay
authors: Paolo
authors: P
authors: Airo'
authors: Marieke J
authors: MJ
authors: Coenen
authors: Kelly
authors: K
authors: Tsang
authors: Antonios O
authors: AO
authors: Aliprantis
authors: Javier
authors: J
authors: Martin
authors: Yannick
authors: Y
authors: Allanore
authors: Timothy R D J
authors: TR
authors: Radstake
mesh_terms: D000328:Adult; D000368:Aged; D005060:Europe; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D053660:Receptors, Interleukin-13 / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology
chemical_list: C504000:IL4R protein, human; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D053660:Receptors, Interleukin-13; D015847:Interleukin-4