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A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA

Author

Listed:
  • Ana Márquez
  • Roser Solans
  • José Hernández-Rodríguez
  • Maria C Cid
  • Santos Castañeda
  • Marc Ramentol
  • Luis Rodriguez-Rodriguez
  • Javier Narváez
  • Ricardo Blanco
  • Norberto Ortego-Centeno
  • Spanish GCA Consortium
  • Øyvind Palm
  • Andreas P Diamantopoulos
  • Niko Braun
  • Frank Moosig
  • Torsten Witte
  • Lorenzo Beretta
  • Claudio Lunardi
  • Marco A Cimmino
  • Augusto Vaglio
  • Carlo Salvarani
  • Miguel A González-Gay
  • Javier Martín

Abstract

Introduction: Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. Methods: A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays. Results: A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (PMH = 0.041, OR = 0.88, CI 95% 0.78–0.99) and recessive (PMH = 3.40E-03, OR = 0.53, CI 95% 0.35–0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis. Conclusions: Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA.

Suggested Citation

  • Ana Márquez & Roser Solans & José Hernández-Rodríguez & Maria C Cid & Santos Castañeda & Marc Ramentol & Luis Rodriguez-Rodriguez & Javier Narváez & Ricardo Blanco & Norberto Ortego-Centeno & Spanish , 2014. "A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-7, November.
    • Handle: RePEc:plo:pone00:0113476
    DOI: 10.1371/journal.pone.0113476
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    1. Adaikalavan Ramasamy & Mikko Kuokkanen & Sailaja Vedantam & Zofia K Gajdos & Alexessander Couto Alves & Helen N Lyon & Manuel A R Ferreira & David P Strachan & Jing Hua Zhao & Michael J Abramson & Mat, 2012. "Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA," PLOS ONE, Public Library of Science, vol. 7(9), pages 1-10, September.
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