PTPN22 Genotype, 1858C->T
Identifying individuals previously diagnosed with rheumatoid arthritis who may be at increased risk for developing more severe, erosive articular disease
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by joint inflammation and destruction. It is heterogeneous, with genetic and environmental factors contributing to its development.(1) There is a well-established link between an increased risk of developing RA and specific alleles of the human leukocyte antigen (HLA) complex including HLA-DRB1*0404, HLA-DRB1*0405, and HLA-DRB1*0101. It has been estimated that those HLA alleles are responsible for approximately 50% of the genetic susceptibility to RA.(1)
Recently, other genes have been identified that also influence the susceptibility of an individual to developing RA. The gene PTPN22 (protein tyrosine phosphatase, non-receptor type 22) encodes the protein Lyp, a phosphatase that is responsible, in part, for regulating T-cell activation. A particular single nucleotide polymorphism (SNP) in PTPN22, designated as 1858C->T, is found more frequently in individuals with autoimmune diseases, including RA, than in healthy control cohorts.(2) It has been proposed that the 1858C->T SNP alters the function of the Lyp, rendering the individual more susceptible to developing RA.(2) In addition, in patients diagnosed with RA, the presence of the T allele has been linked to certain disease phenotypes, including positivity for cyclic citrullinated peptide (CCP) antibodies (a marker for RA), earlier age at diagnosis, and increased rate of joint erosion.(3)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
In individuals with rheumatoid arthritis, the presence of the T allele, either as a C/T heterozygote or as a T/T homozygote, suggests an increased risk for the development of more severe articular disease. Individuals who are homozygous for the C allele (C/C) may have a less aggressive disease course.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not to be used for the diagnosis of rheumatoid arthritis (RA). The diagnosis of RA should be based on clinical evaluation, with supporting evidence from serologic and radiographic studies.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
Blood transfusions or bone marrow transplantation prior to having blood drawn for DNA analysis can generate false results, as the specimen may contain a mix of patient and donor DNA.
In a study conducted at Mayo Clinic, 98 patients with rheumatoid arthritis (RA) and 99 healthy controls were genotyped for the PTPN22 1858C->T polymorphism. The T polymorphism was associated with RA, with at least 1 copy of the T allele being detected in 31% of the patients with RA as compared to 13% of the healthy control individuals (p=0.004). Within the RA cohort, the genotype data was correlated to clinical phenotypes. Individuals who possessed at least 1 copy of the T allele had a younger age at diagnosis (45.2 +/- 13.8 years) than C/C homozygotes (50.5 +/- 14.0 years) (p=0.09). Surgical joint replacement was required in 45% of the patients who carried the T allele in comparison to 21% of patients who lacked the T allele (p=0.013). In addition, patients who possessed the T polymorphism were more likely to have been treated with an antitissue necrosis factor (TNF) agent (61%) in comparison to the C/C homozygous patients (39%) (p=0.038).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003 May; 423(6937):356-361
2. Begovich AB, Carlton VE, Honigberg LE, et al: A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 2004 Aug; 75(2): 330-337
3. Lie BA, Viken MK, Odegard S, et al: Associations between the PTPN22 1858C-T polymorphism and radiographic joint destruction in patients with rheumatoid arthritis: Results from a 10-year longitudinal study. Ann Rheum Dis. 2007 Dec; 66(12):1604-1609