Abstract: Objectives: CD226 genetic variants have been associated with a number of autoimmune diseases. The aim of this study was to investigate the potential implication of the CD226 loci in the susceptibility to and main clinical manifestations of giant cell arteritis (GCA). Methods: A Spanish Caucasian cohort of 455 patients diagnosed with biopsy-proven GCA and 1414 healthy controls were included in the study. Three CD226 polymorphisms, rs727088, rs34794968 and rs763361, were genotyped using the TaqMan® allelic discrimination technology. PLINK software was used for the statistical analyses. Results: No significant association between the CD226 polymorphisms and susceptibility to GCA was found (rs727088: p=0.92, OR=1.01, CI 95% 0.86?1.18; rs34794968: p=0.61, OR=1.04, CI 95% 0.89?1.22; rs763361: p=0.88, OR=0.99, CI 95% 0.84?1.16). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischaemic manifestations or irreversible occlusive disease, no association was observed either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. Furthermore, the haplotype analysis revealed no significant association with the clinical manifestations of the disease. Conclusions: Our results show that the three D226 polymorphisms analysed do not play a relevant role in the susceptibility to GCA and clinical manifestations of this vasculitis.

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