2290 The Journal of Rheumatology 2011; 38:11; doi:10.3899/jrheum.110361 Personal non-commercial use only. The Journal of Rheumatology Copyright © 2011. All rights reserved. Evidence for PTPN22 R620W Polymorphism As the Sole Common Risk Variant for Rheumatoid Arthritis in the 1p13.2 Region JOSE-EZEQUIEL MARTÍN, BEHROOZ Z. ALIZADEH, MIGUEL A. GONZÁLEZ-GAY, ALEJANDRO BALSA, DORA PASCUAL-SALCEDO, MARÍA F. GONZÁLEZ-ESCRIBANO, LUIS RODRIGUEZ-RODRIGUEZ, BENJAMÍN FERNÁNDEZ-GUTIÉRREZ, ENRIQUE RAYA, MARIEKE J.H. COENEN, PIET van RIEL, TIMOTHY R.D.J. RADSTAKE, TORE K. KVIEN, MARTE K. VIKEN, BENEDICTE A. LIE, BOBBY P.C. KOELEMAN, and JAVIER MARTÍN ABSTRACT. Objective. The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region. Methods. We analyzed Wellcome Trust Case-Control Consortium genome-wide association study data for associations in the 397.2 kb PTPN22 region and selected 9 associated SNP (with p < 5 × 10 –3 ) for replication and dependence analysis. The replication cohorts comprised 2857 patients with RA and 2994 controls from Spain, Netherlands, and Norway. Results. We found that 6 of the 9 selected SNP were associated in the Spanish cohort. Of these, 4 were also associated in the Dutch and Norwegian cohorts, and all 6 were associated with RA in the combined analysis. Conditional analyses showed that none of these associations was independent of rs2476601. Conclusion. The SNP rs2476601 located in the PTPN22 gene is the sole common genetic variant asso- ciated with RA in the 1p13.2 region, suggesting that neighbor genes of PTPN22 do not have a major influence in RA. (First Release Oct 1 2011; J Rheumatol 2011;38:2290–6; doi:10.3899/jrheum.110361) Key Indexing Terms: PTPN22 GENETIC SUSCEPTIBILITY RHEUMATOID ARTHRITIS LOGISTIC REGRESSION From the Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain; Department of Epidemiology, University Medical Centre Groningen, Groningen, The Netherlands; Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain; Department of Rheumatology and Department of Immunology, Hospital La Paz, Madrid, Spain; Department of Immunology, Hospital Virgen del Rocio, Seville, Spain; Department of Rheumatology, Hospital Clinico San Carlos, Madrid, Spain; Department of Rheumatology, Hospital Universitario Clinico San Cecilio, Granada, Spain; Department of Human Genetics and Department of Rheumatology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands; Department of Rheumatology, Diakonhjemmet Hospital, Oslo; Institute of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway; and Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands. Supported by grant SAF2009-11110 and by Junta de Andalucía grant CTS-4977; and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+I 2008-2011 (FEDER). Dr. Koeleman is supported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). Dr. Lie is supported by the Research Council of Norway. J-E. Martín, BSc, Instituto de Parasitología y Biomedicina López-Neyra, CSIC; B.Z. Alizadeh, PhD, Department of Epidemiology, University Medical Centre Groningen; M.A. González-Gay, MD, PhD, Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV; A. Balsa, MD, PhD, Department of Rheumatology, Hospital La Paz; D. Pascual-Salcedo, MD, PhD, Department of Immunology, Hospital La Paz; M.F. González-Escribano, MD, PhD, Department of Immunology, Hospital Virgen del Rocio; L. Rodriguez-Rodriguez, MD, PhD; B. Fernández-Gutiérrez, MD, PhD, Department of Rheumatology, Hospital Clinico San Carlos; E. Raya, MD, PhD, Department of Rheumatology, Hospital Universitario Clinico San Cecilio; M.J.H. Coenen, PhD, Department of Human Genetics, Radboud University; P. van Riel, MD, PhD; T.R.D.J. Radstake, MD, PhD, Department of Rheumatology, Radboud University, Nijmegen Medical Center; T.K. Kvien, MD, PhD, Department of Rheumatology, Diakonhjemmet Hospital; M.K. Viken, MD, PhD; B.A. Lie, MD, PhD, Institute of Immunology, Oslo University Hospital Rikshospitalet; B.P.C. Koeleman, PhD, Department of Medical Genetics, University Medical Centre Utrecht; J. Martín, MD, PhD, Instituto de Parasitología y Biomedicina López-Neyra, CSIC. B.P.C. Koeleman and J. Martín contributed equally to this report. Address correspondence to J-E. Martín, Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Parque Tecnologico de Ciencias de la Salud, Avenida del Conocimiento s/n 18100 Armilla, Granada, Spain. E-mail: cebercoto@ipb.csic.es Accepted for publication July 13, 2011. More than 100 genetic variants are now unambiguously asso- ciated with complex human autoimmune diseases 1 . In recent years several genome-wide association studies (GWAS) have been carried out on rheumatoid arthritis (RA), giving rise to a number of new genetic associations 2,3,4,5,6 . Nevertheless, association of a genetic variation does not mean causal asso- ciation of the variant with the disease. The most common sce- nario is that a single-nucleotide polymorphism (SNP) shows association with the trait because it is in linkage disequilibri- um with the causal variant. www.jrheum.org Downloaded on January 15, 2023 from