title: 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.
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 x 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.
authors.affiliation: Rowe Program in Genetics, Departments of Biochemistry and Medicine, University of California-Davis, Davis, CA, USA. mdfseldin@ucdavis.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Seldin
authors.forename: R
authors.initials: R
authors.lastname: Shigeta
authors.forename: K
authors.initials: K
authors.lastname: Laiho
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Saila
authors.forename: A
authors.initials: A
authors.lastname: Savolainen
authors.forename: M
authors.initials: M
authors.lastname: Leirisalo-Repo
authors.forename: K
authors.initials: K
authors.lastname: Aho
authors.forename: E
authors.initials: E
authors.lastname: Tuomilehto-Wolf
authors.forename: K
authors.initials: K
authors.lastname: Kaarela
authors.forename: M
authors.initials: M
authors.lastname: Kauppi
authors.forename: H C
authors.initials: HC
authors.lastname: Alexander
authors.forename: A B
authors.initials: AB
authors.lastname: Begovich
authors.forename: J
authors.initials: J
authors.lastname: Tuomilehto
mesh_terms: D000483:Alleles; D001171:Arthritis, Juvenile / Q000453:epidemiology / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D009679:Nuclear Family; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases