Association of a functional single-nucleotide polymorphism of PTPN22, encoding lymphoid protein phosphatase, with rheumatoid arthritis and systemic lupus erythematosus

Arthritis Rheum. 2005 Jan;52(1):219-24. doi: 10.1002/art.20771.

Abstract

Objective: To assess the possible association between the PTPN22 gene 1858C-->T polymorphism and the predisposition and clinical expression of 2 systemic autoimmune diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Methods: Our study population consisted of 826 RA patients, 338 SLE patients, and 1,036 healthy subjects. All subjects were of Spanish Caucasian origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay.

Results: The overall distribution of genotypes in the RA patients was significantly different from that in the controls (P = 0.005, by chi-square test with 2 x 3 contingency tables). We observed a statistically significant difference in the distribution of the PTPN22 1858T allele between healthy subjects (7.4%), and RA patients (10.4%) (P = 0.001, odds ratio [OR] 1.45 [95% confidence interval (95% CI) 1.15-1.83]). In addition, PTPN22 1858 C/T and T/T genotypes were present at a significantly higher frequency in SLE patients than in controls (P = 0.02, OR 1.55 [95% CI 1.05-2.29]). Differences were also observed when allele frequencies were compared, with the PTPN22 1858T allele being present at a higher frequency among SLE patients (P = 0.03, OR 1.45 [95% CI 1.01-2.09]).

Conclusion: These results suggest that the PTPN22 1858T allele may confer differential susceptibility to RA and SLE in the Spanish population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / genetics*
  • Cytosine
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / genetics*
  • Lymphoid Tissue / enzymology*
  • Male
  • Middle Aged
  • Nephritis / etiology
  • Phosphoprotein Phosphatases / genetics*
  • Polymorphism, Single Nucleotide*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases / genetics*
  • Thymine

Substances

  • Cytosine
  • Phosphoprotein Phosphatases
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22
  • Protein Tyrosine Phosphatases
  • Thymine