PTPN22 Genotype, 1858C->T
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Identifying individuals previously diagnosed with rheumatoid arthritis who may be at increased risk for developing more severe, erosive articular disease
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) 5'-Nuclease End point Allelic Discrimination Analysis
(PCR is utilized pursuant to a license agreement with Roche Molecular System, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
PTPN22 Genotype, 1858C>T
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple whole blood EDTA genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send specimen in original tube.
1. Bone marrow and liver transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
2. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Ambient (preferred)|
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
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. Genotyping for the 1858C->T allele is performed using a PCR-based 5'-nuclease assay. Fluorescently-labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the polymorphism. If the detection probe is an exact match to the target DNA, the 5'-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected. A genotype is assigned based on the allele-specific fluorescent signals that are detected. (Package insert: Taqman SNP Genotyping Assay, Applied Biosystems)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Tuesday; 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 2 weeks Extracted DNA: 2 months
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479 -Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|31757||PTPN22 Genotype, 1858C>T||In Process|
|31758||PTPN22 Interpretation||In Process|
|31759||PTPN22 Reviewed by||In Process|