title: Influence of the IL17A locus in giant cell arteritis susceptibility.
abstract: OBJECTIVE
  Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes.
  
  
  METHODS
  We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed.
  
  
  RESULTS
  In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)).
  
  
  CONCLUSIONS
  Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Márquez
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: J
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: M C
authors.initials: MC
authors.lastname: Cid
authors.affiliation: Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Solans
authors.affiliation: Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Department of Pathology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Fernández-Contreras
authors.affiliation: Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ramentol
authors.affiliation: Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: I C
authors.initials: IC
authors.lastname: Morado
authors.affiliation: Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Narváez
authors.affiliation: Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Gómez-Vaquero
authors.affiliation: Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
authors.forename: V M
authors.initials: VM
authors.lastname: Martínez-Taboada
authors.affiliation: Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Ortego-Centeno
authors.affiliation: Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Pontevedra, Vigo, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Sopeña
authors.affiliation: Department of Rheumatology, Grup de recerca cel·lular en inflamació i cartílag, IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Monfort
authors.affiliation: Department of Rheumatology, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: García-Villanueva
authors.affiliation: Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Caminal-Montero
authors.affiliation: Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: de Miguel
authors.affiliation: Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Palm
authors.affiliation: Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Molberg
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Latus
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Braun
authors.affiliation: Department of Clinical Immunology and Rheumatology, University of Luebeck, Bad Bramstedt, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Moosig
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: T
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: L
authors.initials: L
authors.lastname: Beretta
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santaniello
authors.affiliation: Unita` Operativa di Reumatologia, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pazzola
authors.affiliation: Unita` Operativa di Reumatologia, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Boiardi
authors.affiliation: Unita` Operativa di Reumatologia, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Salvarani
authors.affiliation: Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: González-Gay
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martín
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D013700:Giant Cell Arteritis / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17
keywords: Cytokines; Gene Polymorphism; Giant Cell Arteritis