Influence of the IL17A locus in giant cell arteritis susceptibility.
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.
['Márquez|A|A|', 'Hernández-Rodríguez|J|J|', 'Cid|M C|MC|', 'Solans|R|R|', 'Castañeda|S|S|', 'Fernández-Contreras|M E|ME|', 'Ramentol|M|M|', 'Morado|I C|IC|', 'Narváez|J|J|', 'Gómez-Vaquero|C|C|', 'Martínez-Taboada|V M|VM|', 'Ortego-Centeno|N|N|', 'Sopeña|B|B|', 'Monfort|J|J|', 'García-Villanueva|M J|MJ|', 'Caminal-Montero|L|L|', 'de Miguel|E|E|', 'Blanco|R|R|', '|||', 'Palm|O|O|', 'Molberg|O|O|', 'Latus|J|J|', 'Braun|N|N|', 'Moosig|F|F|', 'Witte|T|T|', 'Beretta|L|L|', 'Santaniello|A|A|', 'Pazzola|G|G|', 'Boiardi|L|L|', 'Salvarani|C|C|', 'González-Gay|M A|MA|', 'Martín|J|J|']
D016022:Case-Control Studies D005787:Gene Frequency D020022:Genetic Predisposition to Disease D005838:Genotype D013700:Giant Cell Arteritis D006239:Haplotypes D006801:Humans D020381:Interleukin-17 D011110:Polymorphism, Genetic
Giant Cell Arteritis Cytokines Gene Polymorphism