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Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis
- Source :
- Dipòsit Digital de la UB, Universidad de Barcelona, Recercat. Dipósit de la Recerca de Catalunya, instname
- Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- Immunology
Giant Cell Arteritis
Biology
Genetic polymorphisms
Real-Time Polymerase Chain Reaction
Polymorphism, Single Nucleotide
General Biochemistry, Genetics and Molecular Biology
Article
PTPN22
CSK Tyrosine-Protein Kinase
Cohort Studies
Rheumatology
Gene Frequency
Polymorphism (computer science)
immune system diseases
medicine
Genetics
Immunology and Allergy
Humans
Genetic Predisposition to Disease
skin and connective tissue diseases
Allele frequency
Arteritis de cèl·lules gegants
Giant cell arteritis
Polymorphism, Genetic
Polimorfisme genètic
Case-control study
Protein Tyrosine Phosphatase, Non-Receptor Type 22
medicine.disease
src-Family Kinases
Case-Control Studies
Cohort
Population study
Gene polymorphism
Genètica
Subjects
Details
- ISSN :
- 14682060
- Volume :
- 72
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Annals of the rheumatic diseases
- Accession number :
- edsair.doi.dedup.....f533be7475fbd7bd143053fc944476b7