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Ann Rheum Dis. 2013 Nov;72(11):1882-1886. doi: 10.1136/annrheumdis-2013-203641. Epub 2013 Aug 14.

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

Author information

1
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
2
NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, West Yorkshire, UK.
3
Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain.
4
Department of Rheumatology, Hospital Xeral-Calde, Lugo, Spain.
5
Vasculitis Research Unit, Department of Autoimmune and Systemic Diseases, Hospital Clinic, University of Barcelona, Centre de Recerca Biomèdica Cellex (IDIBAPS), Barcelona, Spain.
6
Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain.
7
Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain.
8
Department of Rheumatology, Hospital Universitario de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
9
Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain.
10
Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Spain.
11
Department of Rheumatology, Hospital Ramón y Cajal, Madrid, Spain.
12
Department of Rheumatology, Grup de recerca cellular en inflamació i cartílag. IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain.
13
Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain.
14
Department of Internal Medicine, Hospital de Galdakano, Vizcaya, Spain.
15
Department of Internal Medicine, Corporació Sanitaria Parc Taulí, Instituto Universitario Parc Taulí, UAB, Sabadell, Barcelona, Spain.
16
Department of Rheumatology, Hospital Universitario 12 de Octubre, Madrid.
17
Department of Rheumatology, Hospital Universitario de La Paz, Madrid, Spain.
18
Department of Rheumatology, Hospital Clínico Universitario San Cecilio, Granada.
19
Department of Internal Medicine, Division of Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany.
20
Department of Rheumatology, Oslo University Hospital, Oslo, Norway and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
21
Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway.
22
Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.
23
Department of Clinical Immunology and Rheumatology, University of Luebeck, Bad Bramstedt, Germany.
24
Hannover Medical School, Hannover, Germany.
#
Contributed equally

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.

KEYWORDS:

Gene Polymorphism; Giant Cell Arteritis; Polymyalgia Rheumatica

PMID:
23946333
PMCID:
PMC4053592
DOI:
10.1136/annrheumdis-2013-203641
[Indexed for MEDLINE]
Free PMC Article

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