Serrano, AuroraMárquez, AnaMackie, Sarah L.Carmona, F. DavidSolans, RoserMiranda-Filloy, José A.Hernández Rodríguez, JoséCid Xutglà, M. CintaCastañeda, SantosMorado, Inmaculada C.Narváez García, Francisco JavierBlanco, RicardoSopeña, BernardoGarcía-Villanueva, María JesúsMonfort, JordiOrtego Centeno, NorbertoUnzurrunzaga, AinhoaMarí-Alfonso, BegoñaSánchez-Martin, JulioMiguel, Eugenio deMagro Checa, CesarRaya, EnriqueBraun, NikoLatus, J.Molberg, O.Lie, Benedicte A.Moosig, FrankWitte, TorstenMorgan, Ann W.González-Gay, Miguel A.Martín, Javier2015-12-112015-12-1120130003-4967https://hdl.handle.net/2445/68401Objective: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). Methods: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. Results: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). Conclusions: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.5 p.application/pdfeng(c) BMJ Publishing Group, 2013Arteritis de cèl·lules gegantsPolimorfisme genèticGenèticaGiant cell arteritisGenetic polymorphismsGeneticsinfo:eu-repo/semantics/article6410812015-12-11info:eu-repo/semantics/openAccess23946333