PTPN22 1858C>T polymorphism is strongly associated with rheumatoid arthritis but not with a response to methotrexate therapy.

Abstract

PTPN22 (protein tyrosine phosphatase non-receptor type 22) 1858C>T single-nucleotide polymorphism (SNP) is one of the genetic risk factors of rheumatoid arthritis (RA). However, its role in the response of RA patients to therapy is not known. We examined a possible association of this SNP with a response of RA patients to methotrexate (MTX) treatment. RA was diagnosed in 371 patients according to the American College of Rheumatology (ACR) criteria. All 371 patients were typed for PTPN22 1858C>T SNP. Clinical data for 308 patients treated with MTX were available. Clinical improvement was evaluated according to the ACR 20% response criteria. Five hundred and forty three unrelated healthy individuals served as a control group. DNA was isolated from venous blood and 1858C>T SNP was established by polymerase chain reaction followed by restriction fragment length polymorphism using XcmI digestion. One hundred and seventy four patients responded to MTX with remission of symptoms, whereas 134 individuals were not responding. Although 78.6% of patients with 1858TT genotype responded to MTX in contrast to 49.5% and 58.1% of CT and CC genotype bearers, respectively, this difference was nonsignificant due to very low numbers of TT homozygotes in both groups of patients. We confirmed strong association of 1858T allele with RA and with a disease limited to joints, but did not observe any association with a lack of rheumatoid factor, described earlier for a smaller population sample. However, the response of RA patients to MTX treatment does not seem to depend on this SNP.

• Authors: Edyta Majorczyk, Andrzej Pawlik, Piotr Kuśnierczyk
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 10 Issue 12 Pg. 1626-9 (Dec 2010) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 20888443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Antirheumatic Agents
• PTPN22 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 22
• Methotrexate

Topics

• Antirheumatic Agents (administration & dosage, therapeutic use)
• Arthritis, Rheumatoid (drug therapy, enzymology, epidemiology, genetics)
• Case-Control Studies
• Female
• Humans
• Male
• Methotrexate (administration & dosage, therapeutic use)
• Middle Aged
• Polymorphism, Single Nucleotide
• Protein Tyrosine Phosphatase, Non-Receptor Type 22 (genetics)
• Treatment Outcome