Finnish case–control and family studies support PTPN22 R620W polymorphism as a risk factor in rheumatoid arthritis, but suggest only minimal or no effect in juvenile idiopathic arthritis

• Published in: Genes and immunity Vol. 6; no. 8; pp. 720 - 722
• Main Authors: Seldin, M F, Shigeta, R, Laiho, K, Li, H, Saila, H, Savolainen, A, Leirisalo-Repo, M, Aho, K, Tuomilehto-Wolf, E, Kaarela, K, Kauppi, M, Alexander, H C, Begovich, A B, Tuomilehto, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2005; Nature Publishing Group
• Subjects: Alleles; Arthritis, Juvenile - epidemiology; Arthritis, Juvenile - genetics; Arthritis, Rheumatoid - epidemiology; Arthritis, Rheumatoid - genetics; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Case-Control Studies; Cohort Studies; Confidence Intervals; Family studies; Finland - epidemiology; Gene Expression; Gene Frequency; Genes; Genetic aspects; Genetic polymorphisms; Genetic Variation; Genetics, Population; Health aspects; Homozygotes; Hospitals; Human Genetics; Immunology; Juvenile arthritis; Kinases; Nuclear Family; Odds Ratio; Phosphatase; Polymorphism; Polymorphism, Genetic; Population control; Population genetics; Population studies; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Protein Tyrosine Phosphatases - genetics; Protein-tyrosine-phosphatase; Public health; Regression analysis; Rheumatoid arthritis; Rheumatoid factor; Risk Factors; Subpopulations; Susceptibility; Finland; United States; United States > US; juvenile idiopathic arthritis; rheumatoid arthritis; PTPN 22
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6364255

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.