We genotyped 525 independent North American white individuals with systemic lupus erythematosus (SLE) for the PTPN22 R620W polymorphism and compared the results with data generated from 1,961 white control individuals. The R620W SNP was associated with SLE (genotypic P = .00009), with estimated minor (T) allele frequencies of 12.67% in SLE cases and 8.64% in controls. A single copy of the T allele (W620) increases risk of SLE (odds ratio [OR] = 1.37; 95% confidence interval [CI] 1.07-1.75), and two copies of the allele more than double this risk (OR = 4.37; 95% CI 1.98-9.65). Together with recent evidence showing association of this SNP with type 1 diabetes and rheumatoid arthritis, these data provide compelling evidence that PTPN22 plays a fundamental role in regulating the immune system and the development of autoimmunity.
Bibliographical noteFunding Information:
We thank all the individuals with SLE, family members, and referring physicians for their ongoing participation in this work. We also thank Catherine Jensen, Neil Wenberg, and Thearith Koueth for technical assistance. This study was supported by grants (R01 AR32274, R01 AR43727) and contracts from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases, Johns Hopkins General Clinical Research Center grant MO1-RR00052, and grants from the Minnesota Lupus Foundation, the Mary Kirkland Center for Lupus Research, and the Alliance for Lupus Research.