title: Differential association of the PTPN22 coding variant with autoimmune diseases in a Dutch population.
abstract: Protein tyrosine phosphatase PTPN22 is involved in the negative regulation of T-cell responsiveness. Recently, the association of a coding variant of the PTPN22 gene-R620W(1858C>T) with a number of autoimmune diseases has been described. Therefore, we tested the association of PTPN22 1858*T allele in Dutch early onset type 1 diabetes (T1D) and rheumatoid arthritis (RA) patients, as well as celiac disease (CD) patients, for which no previous study of PTPN22 has been reported. The PTPN22 variant was strongly associated with T1D in cases vs controls (P=2 x 10(-7), OR=2.3, 95% CI=1.7-3.1) as well as in a transmission disequilibrium test in nuclear trio's (P=9 x 10(-9), OR=3.3, CI=2.1-5.0), RA (case/control: P=0.003, OR=1.8 CI =1.2-2.6), but not CD, in spite of a trend of increased homozygosity (P=0.05) and early age at onset (P=0.01). PTPN22 is not generally associated with T-cell mediated autoimmune diseases, although it might play a role in the CD patients with early clinical manifestation.
authors.affiliation: Division of Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Zhernakova
authors.forename: P
authors.initials: P
authors.lastname: Eerligh
authors.forename: C
authors.initials: C
authors.lastname: Wijmenga
authors.forename: P
authors.initials: P
authors.lastname: Barrera
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
authors.forename: B P C
authors.initials: BP
authors.lastname: Koeleman
mesh_terms: D000293:Adolescent; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics*; D002446:Celiac Disease / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D009426:Netherlands; D011110:Polymorphism, Genetic; D011153:Population / Q000235:genetics; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases