Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Analysis of the Influence of PTPN22 Gene Polymorphisms in Systemic Sclerosis.
Diaz-Gallo7, Lina Marcela, Gourh27, Pravitt, Broen4, Jasper, Simeon16, Carmen, Fonollosa16, Vicent, Ortego-Centeno13, Norberto, Vonk4, M. C.
Department of Dermatology, University of Cologne, Germany
Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundation Trust, UK
Rheumatology Department, Universite Catholique de Louvain
Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain
Servicio de Medicina Interna, Hospital Clinico Universitario, Granada, Spain
Servicio de Medicina Interna, Hospital Clinico, Barcelona, Spain
Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Oviedo, Spain
Servicio de Medicina Interna, Hospital Valle de Hebron, Barcelona, Spain
Servicio de Medicina Interna. Hospital Virgen del Rocio, Sevilla, Spain
Servicio de Reumatología, Hospital 12 de Octubre, Madrid, Spain
Servicio de Reumatología, Hospital Carlos Haya, Málaga, Spain
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin
Servicio de Reumatología, Hospital de Sant Pau, Barcelona, Spain
Servicio de Reumatología, Hospital del Mar, Barcelona, Spain
Servicio de Reumatología, Hospital Marques de Valdecillas, Santander, Spain
Servicio de Reumatología, Hospital Ramon y Cajal, Madrid, Spain
Servicio de Reumatología. Hospital Reina Sofía, Córdoba, Spain
Servizio di Reumatologia ed Immunologia Clinica Spedali Civili, Brescia, Italy
The University of Texas Health Science Center at Houston Medical School, Department of Internal Medicine, Division of Rheumatology and Clinical Immunogenetics
The University of Texas Health Science Center at Houston Medical School, Department of Internal Medicine, Division of Rheumatology and Clinical Immunogenetics.
The University of Texas Health Science Center at San Antonio, San Antonio, TX
University of Ghent, Belgium
Department of Rheumatology, Lund University Hospital, Lund, Sweden
University of Texas Medical Branch at Galveston, Galveston, TX
Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Departmentof Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Hannover Medical School, Hannover, Germany
Instituto de Parasitología y Biomedicina Lopez-Neyra CSIC, Granada, Spain
Referral Center for Systemic Autoimmune Diseases, University of Milan, Milan, Italy
Rheumatic Diseases Centre, University of Manchester, Salford Royal NHS Foundatin Trust, UK
Two functional single nucleotide polymorphisms (SNPs) in the PTPN22 gene (R620W, C1858T, rs24746601; and R263Q, G788A, rs33996649) have been previously associated with autoimmune diseases. The aim of the present study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W PTPN22 polymorphism in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes.
A total of 3422 SSc patients (2020 with limited cutaneous SSc (lcSSc) and 1208 with diffuse cutaneous SSc (dcSSc)) and 3638 healthy controls from an initial case-control set of Spanish Caucasian ancestry, as well as seven independent replication cohorts of Caucasian ancestry (from Belgium, England, Germany, Italy, the Netherlands, USA and Sweden), were included in our study. Genotyping was performed using the TaqMan allelic discrimination assay for both the rs33996649 and the rs2476601 PTPN22 polymorphisms. A meta-analysis was then performed to test the overall effect of these PTPN22 gene polymorphisms in SSc.
We observed evidence of association of the rs2476601 T allele with SSc susceptibility in the meta-analysis results (P=0.01 pooled, OR=1.15, 95% CI 1.031.28). Moreover, the rs2476601 T allele is significantly associated with anti-centromere (ACA) positive status (P=0.01 pooled, OR=1.22, 95% CI 1.051.42). Although we found that the rs33996649 A allele was significantly associated with SSc in the Spanish population (P=0.02, OR=0.58, 95% CI 0.360.92), this association was not confirmed in the meta-analysis (P=0.36 pooled, OR=0.89, 95% CI 0.721.1).
Our study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but that the novel R263Q genetic variant does not. Moreover, our data strengthen the evidence that the R620W mutation is a common risk factor in autoimmune diseases.
To cite this abstract, please use the following information:
Diaz-Gallo, Lina Marcela, Gourh, Pravitt, Broen, Jasper, Simeon, Carmen, Fonollosa, Vicent, Ortego-Centeno, Norberto, et al; Analysis of the Influence of PTPN22 Gene Polymorphisms in Systemic Sclerosis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :824