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Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

Diaz-Gallo, L. M.; Gourh, P.; Broen, J.; Simeon, C.; Fonollosa, V.; Ortego-Centeno, N.; Agarwal, S.; Vonk, M. C.; Coenen, M. and Riemekasten, G., et al. (2011) In Annals of the Rheumatic Diseases 70(3). p.454-462
Abstract
Objective Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination... (More)
Objective Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected) = 0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected) = 0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected) = 0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p = 0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases. (Less)
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published
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Annals of the Rheumatic Diseases
volume
70
issue
3
pages
454 - 462
publisher
British Medical Association
external identifiers
  • wos:000286927800009
  • scopus:79951512546
ISSN
1468-2060
DOI
10.1136/ard.2010.130138
language
English
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yes
id
e78cfdc5-5b44-4cb4-9b81-ea9f6e6e3b38 (old id 1876574)
date added to LUP
2011-04-01 11:22:45
date last changed
2017-10-01 04:16:18
@article{e78cfdc5-5b44-4cb4-9b81-ea9f6e6e3b38,
  abstract     = {Objective Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected) = 0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected) = 0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected) = 0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p = 0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.},
  author       = {Diaz-Gallo, L. M. and Gourh, P. and Broen, J. and Simeon, C. and Fonollosa, V. and Ortego-Centeno, N. and Agarwal, S. and Vonk, M. C. and Coenen, M. and Riemekasten, G. and Hunzelmann, N. and Hesselstrand, Roger and Tan, F. K. and Reveille, J. D. and Assassi, S. and Garcia-Hernandez, F. J. and Carreira, P. and Camps, M. T. and Fernandez-Nebro, A. and Garcia de la Pena, P. and Nearney, T. and Hilda, D. and Gonzalez-Gay, M. A. and Airo, P. and Beretta, L. and Scorza, R. and Herrick, A. and Worthington, J. and Pros, A. and Gomez-Gracia, I. and Trapiella, L. and Espinosa, G. and Castellvi, I. and Witte, T. and de Keyser, F. and Vanthuyne, M. and Mayes, M. D. and Radstake, T. R. D. J. and Arnett, F. C. and Martin, J. and Rueda, B.},
  issn         = {1468-2060},
  language     = {eng},
  number       = {3},
  pages        = {454--462},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis},
  url          = {http://dx.doi.org/10.1136/ard.2010.130138},
  volume       = {70},
  year         = {2011},
}