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Ann Rheum Dis. 2014 Sep;73(9):1742-5. doi: 10.1136/annrheumdis-2014-205261. Epub 2014 Jun 11.

Influence of the IL17A locus in giant cell arteritis susceptibility.

Author information

1
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
2
Vasculitis Research Unit, Department of Autoimmune and Systemic Diseases, Hospital Clinic, University of Barcelona, Centre de Recerca Biomèdica Cellex (IDIBAPS), Barcelona, Spain.
3
Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
4
Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain.
5
Department of Pathology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain.
6
Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain.
7
Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
8
Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
9
Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain.
10
Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Pontevedra, Vigo, Spain.
11
Department of Rheumatology, Grup de recerca cel·lular en inflamació i cartílag, IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain.
12
Department of Rheumatology, Hospital Ramón y Cajal, Madrid, Spain.
13
Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
14
Department of Rheumatology, Hospital Universitario La Paz, Madrid, Spain.
15
Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
16
Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany.
17
Department of Clinical Immunology and Rheumatology, University of Luebeck, Bad Bramstedt, Germany.
18
Hannover Medical School, Hannover, Germany.
19
Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
20
Unita` Operativa di Reumatologia, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.

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.

KEYWORDS:

Cytokines; Gene Polymorphism; Giant Cell Arteritis

PMID:
24919468
DOI:
10.1136/annrheumdis-2014-205261
[Indexed for MEDLINE]
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