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.
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.
Seldin
M F
MF
Rowe Program in Genetics, Departments of Biochemistry and Medicine, University of California-Davis, Davis, CA, USA. mdfseldin@ucdavis.edu
Shigeta
R
R
Laiho
K
K
Li
H
H
Saila
H
H
Savolainen
A
A
Leirisalo-Repo
M
M
Aho
K
K
Tuomilehto-Wolf
E
E
Kaarela
K
K
Kauppi
M
M
Alexander
H C
HC
Begovich
A B
AB
Tuomilehto
J
J
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
D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases