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The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1

Genes & Immunity volume 6, pages 658–662 (2005)Cite this article

Abstract

The gene PTPN22 is located on chromosome 1p13 and encodes a protein tyrosine phosphatase called the lymphoid-specific phosphatase (Lyp). Lyp is expressed in lymphocytes, where it physically associates through its proline-rich motif (called P1) with the SH3 domain of the protein tyrosine kinase Csk, an important suppressor of the Src family of kinases Lck and Fyn, which mediate TCR signaling. Therefore, it is said that interaction between Lyp and Csk enables these effectors to inhibit T-cell activation synergistically. It was reported that a missense single nucleotide polymorphism , R620W (rs2476601), 1858C—>T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals. PTPN22 gene polymorphisms were genotyped in 571 Swedish SLE patients and 1042 healthy controls using TaqMan SNP Genotyping Assay. Differences were observed between cases and control subjects at both the allele (χ2=11.2895;P=0.0007,1df) and genotype (χ2=10.2243;P=0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (χ2=9.5660;P=0.0019). We then analyzed if in patients with renal disorder associations with PDCD1 and PTPN22 were independent. Our data suggest that this appears to be the case although we observed some degree of interaction.

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Acknowledgements

We would like to thank the patients and their relatives for their collaboration in this project and Ludmila Prokunina-Olsson for help with the PD-1.3 data. This work was supported by grants from the Alliance for Lupus Research to MEAR, The Swedish Research Council for Medicine (12673 and 13489), the Clas Groschinski Memorial Foundation, the Swedish Society Against Rheumatism, the Gustaf V:80-year Jubileum Foundation, the Magnus Bergvalls Foundation, the Torsten and Ragnar Söderbergs Foundation, and by grants from ‘Visare Norr’, Samverkansnämden för Norra Regionen. Professor Göran Hallmans and the Blood Bank of Northern Sweden, and Birgitta Stegmayr, PhD, Department of Public Health and Clinical Medicine/Internal Medicine kindly provided control samples from the WHO-MONICA cohort. MEAR is a Fellow at the Royal Swedish Academy of Sciences.

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Authors and Affiliations

  1. Department of Genetics and Pathology, Rudbeck Laboratory, Section of Medical Genetics, Uppsala University, Uppsala, Sweden

    M V Prasad Linga Reddy & M E Alarcón-Riquelme

  2. Department of Rheumatology, University Hospital, Umeå, Sweden

    M Johansson & S Rantapää-Dahlqvist

  3. Department of Rheumatology, Lund University Hospital, Lund, Sweden

    G Sturfelt & A Jönsen

  4. Unit for Rheumatology, Karolinska University Hospital, Solna, Sweden

    I Gunnarsson & E Svenungsson

Authors
  1. M V Prasad Linga Reddy
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  2. M Johansson
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  3. G Sturfelt
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  4. A Jönsen
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  5. I Gunnarsson
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  6. E Svenungsson
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  7. S Rantapää-Dahlqvist
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  8. M E Alarcón-Riquelme
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Correspondence to M E Alarcón-Riquelme.

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Reddy, M., Johansson, M., Sturfelt, G. et al. The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1. Genes Immun 6, 658–662 (2005). https://doi.org/10.1038/sj.gene.6364252

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