1. ¹Rowe Program in Genetics, Departments of Biochemistry and Medicine, University California Davis, Davis, CA, USA
2. ²Rheumatism Foundation Hospital, Heinola, Finland
3. ³Department of Medicine, Helsinki University Hospital, Helsinki, Finland
4. ⁴Department of Health and Disability, National Public Health Institute, Helsinki, Finland
5. ⁵Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland
6. ⁶Celera Diagnostics, Alameda, CA, USA
7. ⁷South Ostrobothnia Central Hospital, Seinajoki, Finland

Correspondence: Dr MF Seldin, Rowe Program in Genetics, Department of Biological Chemistry and Medicine, Room 4453, Tupper Hall, One Shields Avenue, University of California, Davis, CA 95616, USA. E-mail: mfseldin@ucdavis.edu

Received 21 June 2005; Revised 8 July 2005; Accepted 19 July 2005; Published online 18 August 2005.

Abstract

Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes the R620W amino-acid change as a putative susceptibility factor in autoimmune diseases. The current study was undertaken to examine a large cohort of Finnish rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) subjects using both population control and, importantly, family-based association methods. The latter is particularly important when, as is the case for the 1858 C/T polymorphism, the frequency of the variant allele (T) differs in both major ancestral populations and in subpopulations. The analysis of rheumatoid factor-positive 1030 RA probands from Finland provides strong support for association of this variant in both population studies (allele specific odds ratio (OR)=1.47, 95% confidence interval (CI)=1.27–1.70, P=3 10^-7) and in family studies (P<10^-6). In contrast, no allelic association was seen with JIA (230 probands) and only weak evidence for a genotypic effect of 1858T homozygotes was observed in this population.