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

Annals of the Rheumatic Diseases

PubMedID: 23946333

Serrano A, Márquez A, Mackie SL, Carmona FD, Solans R, Miranda-Filloy JA, Hernández-Rodríguez J, Cid MC, Castañeda S, Morado IC, Narváez J, Blanco R, Sopeña B, García-Villanueva MJ, Monfort J, Ortego-Centeno N, Unzurrunzaga A, Marí-Alfonso B, Sánchez-Martín J, De Miguel E, Magro C, Raya E, Braun N, Latus J, Molberg O, Lie BA, Moosig F, Witte T, Morgan AW, González-Gay MA, Martín J, UK GCA Consortium Spanish GCA Consortium. Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis. Ann Rheum Dis. 2013;72(11):1882-6.
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.