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

Reddy, MVPL; Johansson, M; Sturfelt, Gunnar LU ; Jönsen, Andreas LU ; Gunnarsson, I; Svenungsson, E; Rantapaa-Dahlqvist, S and Alarcon-Riquelme, M (2005) In Genes and Immunity 6(8). p.658-662
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... (More)
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 (chi(2) = 11.2895; P = 0.0007,1df) and genotype (chi(2) = 10.2243; P = 0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
polymorphism, Fyn, Lck, PTPN22, Lyp, systemic lupus erythematosus
in
Genes and Immunity
volume
6
issue
8
pages
658 - 662
publisher
Nature Publishing Group
external identifiers
  • pmid:16052172
  • wos:000233656800003
  • scopus:28544444365
ISSN
1476-5470
DOI
10.1038/sj.gene.6364252
language
English
LU publication?
yes
id
81ceecc6-fe85-4a05-b3e2-43ef6500287b (old id 211642)
date added to LUP
2007-10-05 12:36:21
date last changed
2017-07-30 03:37:28
@article{81ceecc6-fe85-4a05-b3e2-43ef6500287b,
  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 (chi(2) = 11.2895; P = 0.0007,1df) and genotype (chi(2) = 10.2243; P = 0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(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.},
  author       = {Reddy, MVPL and Johansson, M and Sturfelt, Gunnar and Jönsen, Andreas and Gunnarsson, I and Svenungsson, E and Rantapaa-Dahlqvist, S and Alarcon-Riquelme, M},
  issn         = {1476-5470},
  keyword      = {polymorphism,Fyn,Lck,PTPN22,Lyp,systemic lupus erythematosus},
  language     = {eng},
  number       = {8},
  pages        = {658--662},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1},
  url          = {http://dx.doi.org/10.1038/sj.gene.6364252},
  volume       = {6},
  year         = {2005},
}