Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis

• Published in: Annals of the rheumatic diseases
• Main Authors: Serrano, Aurora, Márquez, A, Mackie, Sarah L, Carmona, F. David, Solans, Roser, Miranda-Filloy, José A, Hernández Rodríguez, José, Cid Xutglà, M. Cinta, Castañeda, Santos, Morado, Inmaculada C, Narváez García, Francisco Javier, Blanco, Ricardo, Sopeña, Bernardo, García-Villanueva, María Jesús, Monfort, J, Ortego Centeno, Norberto, Unzurrunzaga, Ainhoa, Marí-Alfonso, Begoña, Sánchez-Martin, Julio, Miguel, E. de, Magro, César, Raya, Enrique, Braun, Niko, Latus, J, Molberg, O, Lie, Benedicte A, Moosig, F, Witte, Torsten, Morgan, Ann W, González-Gay, Miguel A, Martin, Javier
• Format: Journal Article
• Language: English
• Published: BMJ Publishing Group 2013
• Subjects: Arteritis de cèl·lules gegants; Genetic polymorphisms; Genetics; Genètica; Giant cell arteritis; Polimorfisme genètic
• ISSN: 0003-4967

Objective: 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.