title: A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA.
abstract: BACKGROUND
  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 (P(MH) = 0.041, OR = 0.88, CI 95% 0.78-0.99) and recessive (P(MH) = 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.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain; Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Márquez
authors.affiliation: Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Solans
authors.affiliation: Vasculitis Research Unit, Department of Autoimmune and Systemic Diseases, Hospital Clinic, University of Barcelona, Centre de Recerca Biomèdica Cellex (IDIBAPS), Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Hernández-Rodríguez
authors.affiliation: Vasculitis Research Unit, Department of Autoimmune and Systemic Diseases, Hospital Clinic, University of Barcelona, Centre de Recerca Biomèdica Cellex (IDIBAPS), Barcelona, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cid
authors.affiliation: Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Ramentol
authors.affiliation: Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.affiliation: Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Narváez
authors.affiliation: Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.affiliation: Department of Rheumatology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Oyvind
authors.initials: O
authors.lastname: Palm
authors.affiliation: Department of Rheumatology, Hospital of Southern Norway Trust, Kristiansand, Norway.
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Diamantopoulos
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany.
authors.forename: Niko
authors.initials: N
authors.lastname: Braun
authors.affiliation: Department of Clinical Immunology and Rheumatology, University of Luebeck, Bad Bramstedt, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Moosig
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.affiliation: Department of Medicine, Università degli Studi di Verona, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.affiliation: Department of Internal Medicine, Academic Unit of Clinical Rheumatology, University of Genova, Genova, Italy.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cimmino
authors.affiliation: Department of Clinical Medicine, Nephrology and Health Sciences, University Hospital of Parma, Parma, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.affiliation: Unità Operativa di Reumatologia, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Salvarani
authors.affiliation: Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D053263:Gene Regulatory Networks; D056426:Genetic Loci; D005838:Genotype; D013700:Giant Cell Arteritis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D012307:Risk Factors
chemical_list: C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D011956:Receptors, Cell Surface