1. ¹Rudbeck Laboratory, Department of Genetics and Pathology, Section of Medical Genetics, Uppsala University, Uppsala, Sweden
2. ²Department of Rheumatology, University Hospital, Umeå, Sweden
3. ³Department of Rheumatology, Lund University Hospital, Lund, Sweden
4. ⁴Unit for Rheumatology, Karolinska University Hospital, Solna, Sweden

Correspondence: Dr ME Alarcon-Riquelme, Rudbeck Laboratory, Department of Genetics and Pathology, Section of Medical Genetics, Uppsala University, 751 85, Uppsala, Sweden. E-mail: marta.alarcon@genpat.uu.se

Received 27 April 2005; Revised 16 June 2005; Accepted 20 June 2005; Published online 4 August 2005.

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 (²=11.2895;P=0.0007,1df) and genotype (²=10.2243;P=0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (²=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.