Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn's disease, in Canadian populations.

Abstract

OBJECTIVE:

A single-nucleotide polymorphism in the PTPN22 gene encoding the lymphoid protein tyrosine phosphatase (Lyp) has recently been identified as a functional variant associated with susceptibility to rheumatoid arthritis (RA), type 1 diabetes, and systemic lupus erythematosus. To determine whether association of this variant (PTPN22 1858T) with RA is reproducible and is also observed in another autoimmune condition, Crohn's disease, we investigated the association between the PTPN22 1858T allele and RA and Crohn's disease in a Canadian population.

METHODS:

Two RA case-control cohorts representing a total of 1,234 patients and 791 healthy controls as well as a cohort of 455 patients with Crohn's disease and 190 controls were genotyped for the PTPN22 C1858T polymorphism, and genotype frequencies were compared between patients and controls.

RESULTS:

Significant association of the PTPN22 1858T allele with RA was detected in both the Toronto-based RA cohort (P = 1.6 x 10(-6), odds ratio [OR] 1.8) and the Halifax-based RA cohort (P = 9.4 x 10(-4), OR 1.94). Association of the risk allele with RA was not affected by sex, age at disease onset, or the presence of either rheumatoid factor or rheumatoid nodules. No association between the PTPN22 risk allele and Crohn's disease was detected.

CONCLUSION:

These observations confirm the association of RA susceptibility with the PTPN22 1858T allele. However, the data also reveal a lack of association between this variant and Crohn's disease, suggesting that the PTPN22 1858T allele is a risk allele for multiple, but not all, autoimmune diseases.

• Authors: Mark van Oene, Richard F Wintle, Xiangdong Liu, Mehrdad Yazdanpanah, Xiangjun Gu, Bill Newman, Albert Kwan, Benjamin Johnson, Julie Owen, Wenda Greer, Dianne Mosher, Walter Maksymowych, Ed Keystone, Laurence A Rubin, Christopher I Amos, Katherine A Siminovitch
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 52 Issue 7 Pg. 1993-8 (Jul 2005) ISSN: 0004-3591 [Print] United States
• PMID: 15986374 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• PTPN22 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatase, Non-Receptor Type 22
• Protein Tyrosine Phosphatases

Topics

• Arthritis, Rheumatoid (epidemiology, genetics, immunology, pathology)
• Canada (epidemiology)
• Case-Control Studies
• Cohort Studies
• Crohn Disease (epidemiology, genetics, immunology, pathology)
• Female
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Genotype
• Humans
• Lymphoid Tissue (enzymology, pathology)
• Male
• Middle Aged
• Molecular Epidemiology
• Odds Ratio
• Polymorphism, Single Nucleotide (genetics)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatase, Non-Receptor Type 22
• Protein Tyrosine Phosphatases (genetics, metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization