HLA-B*5801 Genotype, Allopurinol Hypersensitivity, Blood
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Predicting increased risk of hypersensitivity reactions to allopurinol
Excluding patients at an elevated risk for allopurinol hypersensitivity syndrome from receiving allopurinol
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
Qualitative Allele-Specific Real-Time Polymerase Chain Reaction (PCR)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
HLA-B 5801 Genotype, Allopurinol, B
Allopurinol Hypersensitivity Syndrome (AHS)
Toxic Epidermal Necrolysis
Urate Kidney Stones
Toxic Epidermal Necrolysis
Urate Kidney Stones
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 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.
Additional Information: Patients who had a heterologous blood transfusion within the preceding 45 days (6 weeks), or who have received an allogeneic bone marrow transplant, can have false-genetic test results as human DNA present in the blood may be a mixture of patient and donor DNA. For these patients, a saliva specimen (rather than blood) should be submitted, order HL58O/62153 HLA-B*5801 Genotype, Allopurinol, Saliva.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
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
Allopurinol is widely used for hyperuricemia-related diseases such as gout, Lesch-Nyhan syndrome, and recurrent urate kidney stones. Allopurinol hypersensitivity syndrome is a spectrum of reactions that includes not only Stevens-Johnson syndrome and toxic epidermal necrolysis, but also systemic disease with a clinical constellation of features such as eosinophilia, vasculitis, rash, and major end-organ disease. There is a reported mortality rate of 20% to 25% for allopurinol hypersensitivity syndrome (AHS).
Studies in Han Chinese residing in Taiwan showed that the HLA-B*5801 allele was present in 100% of the patients with allopurinol-induced skin reactions, but in only 15% of allopurinol-tolerant controls. Data obtained from recombinant mapping further concluded that HLA-B*5801 itself is the major susceptibility gene for allopurinol-induced skin reactions in the Han Chinese population. In the Thai population, 100% of patients with allopurinol-induced skin reactions carried the allele, but only 13% of allopurinol-tolerant individuals tested positive for the HLA-B*5801 allele. A similar but more modest 80% of Korean cases compared to 12% of healthy controls and 56% of Japanese cases compared to 0.61% of healthy controls were positive for the HLA-B*5801 allele. Two studies of Europeans have been reported. In the first study, 55% of European cases compared to 1.5% of controls tested positive for the allele and, in the second study, 100% of cases compared to a population frequency of 1.5% were positive for the HLA-B*5801 allele. A meta-analysis that considered all published studies as of the date of the analysis gave the odds ratios for allopurinol-induced severe skin reactions in HLA-B*5801 carriers as 73 and 165 compared to healthy controls and allopurinol-tolerant controls, respectively. The frequency of the HLA-B*5801 allele is widely distributed among other populations: (eg 2%-4% in Africans, 3%-15% in Asian Indians). Further studies are needed to determine if individuals from these populations with this allele are at similar risk for allopurinol hypersensitivity reaction.
Guidelines have been developed by the Clinical Pharmacogenomics Implementation Consortium that recommends that HLA-B*5801 genotyping be performed and that allopurinol should not be prescribed to patients who test positive for the allele. Also, guidelines developed by the 2012 American College of Rheumatology for Management of Gout recommend that HLA-B*5801 testing should be considered in select patient subpopulations at an elevated risk for AHS. Those of Korean descent, especially those with stage 3 or higher chronic kidney disease, or of Han Chinese or Thai extraction irrespective of renal function should be tested. However, given the literature as reviewed above, consideration should be given to testing all patients who will be given allopurinol.
Positivity for HLA-B*5801 confers risk for hypersensitivity to allopurinol
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Rare, unreported HLA-B58 alleles may occur and may or may not interfere with this assay. This assay also detects closely related, but rare, alleles including HLA-B*5705, *5804, *5805, *5809, *5810, *5811, *5812, *5813, *5815, *5817, *5819, *5821, *5822, *5823, *5824 and *5828. There are, as yet, no data indicating whether these subtypes are associated with hypersensitivity.
Allogeneic bone marrow or stem cell transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
Heterologous transfusions of blood that has not been depleted of leukocytes may 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.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Chung WH, Hung SI, Chen YT: Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol 2007;7:317-323
2. Khanna D, Fitzgerald J, Khanna P, et al: 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res 2012;64:1431-1446
3. Hershfield MS, Callaghan JT, Tassaneeyakul W, et al: Clinical Pharmacogenetics Implementation Consortium Guidelines for Human Leukocyte Antigen-B Genotype and Allopurinol Dosing. Clin Pharmacol Ther 2013 Feb;93(2):153-158 Epub ahead of print Oct 2012
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. Amplification for the HLA-B*5801 allele and an internal control gene is performed by real-time PCR in the presence of SYBR green, which fluoresces when bound to double-stranded DNA. A genotype is assigned based on the allele-specific SYBR green fluorescent signals that are detected.(Unpublished Mayo method)
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.
Monday and Thursday
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 using an analyte specific reagent. Its performance characteristics were 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.
81381-HLA Class I typing, high resolution (ie, alleles or allele groups); one allele or allele group (eg, B*57:01P), each
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|
|35101||HLA-B 5801 Result||In Process|
|35102||HLA-B 5801 Interpretation||69965-2|
|35103||Reviewed by||In Process|