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Differential association of the PTPN22 coding variant with autoimmune diseases in a Dutch population

Genes & Immunity volume 6, pages 459–461 (2005)Cite this article

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 × 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 × 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.

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Acknowledgements

We thank all patients and their families participating in the study. We thank physicians participating in the study—Chris Mulder, Roderick Houwen, Maria Luisa Mearin, Jan Bruining. We also thank Alienke Monsuur and Martine van Belzen for the samples collection and Jackie Senior for improving the manuscript. The study was supported by grants from the Dutch Diabetes Research Foundation (97.137), The Dutch Digestive Disease Foundation (WS 03-06), The Netherlands Organisation for Health Research and Development (ZonMW 912-02-028), The Juvenile Diabetes Research Foundation Internationdal (JDRF) (2001.10.004) and the Celiac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK03009).

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Authors and Affiliations

  1. Division of Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands

    A Zhernakova, C Wijmenga & B P C Koeleman

  2. Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands

    P Eerligh, B O Roep & B P C Koeleman

  3. Rheumatology Department, University Hospital St Radboud Nijmegen, The Netherlands

    P Barrera

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  1. A Zhernakova
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  2. P Eerligh
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  3. C Wijmenga
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Correspondence to B P C Koeleman.

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Zhernakova, A., Eerligh, P., Wijmenga, C. et al. Differential association of the PTPN22 coding variant with autoimmune diseases in a Dutch population. Genes Immun 6, 459–461 (2005). https://doi.org/10.1038/sj.gene.6364220

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