Test Catalog

Test Id : HL57R

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HLA-B*57:01 Genotype, Pharmacogenomics, Varies

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying individuals with an increased risk of hypersensitivity reactions to abacavir, based on the presence of the human leukocyte antigen HLA-B*57:01 allele

 

Identifying individuals taking pazopanib who have an increased risk of elevated alanine aminotransferase (ALT) levels based of the presence of the human leukocyte antigen HLA-B*57:01 allele

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Qualitative Allele-Specific Real-Time Polymerase Chain Reaction (PCR)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

HLA-B 5701 Genotype, V

Aliases
Lists additional common names for a test, as an aid in searching

Abacavir Hypersensitivity

Elevated liver function tests

HLA B

HLA B57

HLA B5701

HLA-B57

HLA-B5701

HLAB

HLAB5701

Pazopanib

Pazopanib hepatotoxocity

Pazopanib induced elevated serum transaminases

Pazopanib liver toxicity

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Varies

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List in Special Instructions for a list of tests that can be ordered together. 

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days

 

Specimen Type: Saliva

Supplies: Saliva Swab Collection Kit (T786)

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Specimen Volume: 1 swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

 

Specimen Type: Extracted DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 0.4 mL

Saliva: 1 swab

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying individuals with an increased risk of hypersensitivity reactions to abacavir, based on the presence of the human leukocyte antigen HLA-B*57:01 allele

 

Identifying individuals taking pazopanib who have an increased risk of elevated alanine aminotransferase (ALT) levels based of the presence of the human leukocyte antigen HLA-B*57:01 allele

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The human leukocyte antigen (HLA) genes help the immune system recognize and respond to foreign substances (such as viruses and bacteria). The HLA-B gene encodes a class I HLA molecule in the major histocompatibility complex (MHC), which acts by presenting peptides to immune cells. There are more than 1500 different HLA-B alleles identified, one of which is the HLA-B*57:01 allele. Frequency of the HLA-B*57:01 allele varies with ethnicity, with a frequency of 6% to 7% in European populations and up to 20% in Southwest Asian populations.

 

The HLA-B*57:01 allele has been associated with hypersensitivity to abacavir, a highly effective nucleoside analog reverse-transcriptase inhibitor used to treat HIV infection and AIDS. Per the Clinical Pharmacogenomics Implementation Consortium (CPIC) dosing guidelines for abacavir and HLA-B, individuals who are positive for the HLA-B*57:01 allele are at an increased risk for abacavir hypersensitivity, and it is not recommended for use in treating these individuals.

 

Hypersensitivity reactions, which generally occur during the first 6 weeks of treatment, are often nonspecific and include skin rashes, gastrointestinal symptoms (eg, nausea, vomiting, diarrhea, and abdominal pain), and respiratory symptoms. Fatalities have been reported with abacavir hypersensitivity. Prospective testing for the HLA-B*57:01 genotype and excluding HLA-B*57:01-positive individuals from treatment with abacavir decreases the incidence of abacavir hypersensitivity.

 

Pazopanib is a kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma and advanced soft tissue sarcoma who have received prior chemotherapy. In clinical trials with pazopanib, hepatotoxicity was observed, manifested as increases in serum transaminases such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. This hepatotoxicity can be severe and fatal. Patients older than 65 years are at greater risk for hepatotoxicity. Transaminase elevations occur early in the course of treatment (92.5% of all transaminase elevations of any grade occurred in the first 18 weeks).

 

Patients who are HLA-B*57:01 carriers and are taking pazopanib are at increased risk of elevated ALT levels.(1,2) According to the FDA label for pazopanib, in an analysis of data from 31 clinical studies of pazopanib administered as either monotherapy or in combination with other agents, elevation in ALT to levels greater than 3 times the upper limit of normal occurred in 32% (42/133) of HLA-B*57:01 allele carriers as compared to 19% (397/2101) of noncarriers. Furthermore, elevation in ALT to levels greater than 5 times the upper limit of normal occurred in 19% (25/133) of HLA-B*57:01 allele carriers and in 10% (213/2101) of noncarriers. All patients taking pazopanib should have hepatic function monitored, regardless of HLA-B*57:01 carrier status, and administration of pazopanib should be interrupted, reduced, or discontinued according to recommendations in the FDA label if hepatic function is impaired.

 

UGT1A1 genotype is also relevant to pazopanib-induced hyperbilirubinemia and testing may also be warranted. See U1A1V / UDP-Glucuronosyl Transferase 1A1 TA Repeat Genotype, UGT1A1, Varies.

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.

Negative

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

Positivity for human leukocyte antigen allele HLA-B*57:01 confers high risk for hypersensitivity to abacavir and higher risk of elevated alanine aminotransferase (ALT) levels in patient taking pazopanib.

 

See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Samples may contain donor DNA if obtained from patients who received nonleukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. The impact of hematopoietic stem cell transplantation on risk of abacavir hypersensitivity reactions is not defined in the literature.

 

The FDA recommends screening for the HLA-B*57:01 allele before initiating therapy with abacavir. Genotyping is also critical when there is a clinical history of, or when the physician suspects, an abacavir hypersensitivity reaction. However, FDA guidance states that, regardless of HLA-B*57:01 status, abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Although the negative predictive value of the test is high, a negative HLA-B*57:01 result does not preclude the development of a hypersensitivity response to abacavir and cannot substitute for clinical vigilance whenever abacavir therapy is administered. Since symptoms of abacavir hypersensitivity are often nonspecific and can imitate other conditions commonly seen in HIV patients on antiretroviral therapy, the phenotypic diagnosis of abacavir hypersensitivity can be challenging. There is significant variability among patients identified as hypersensitive to abacavir. Not all individuals who are positive for HLA-B*57:01 will have a hypersensitivity reaction.

 

All patients taking pazopanib should have hepatic function monitored, regardless of HLA-B*57:01 carrier status, and administration of pazopanib should be interrupted, reduced, or discontinued according to recommendations in the FDA label if hepatic function is impaired.

 

Rare or novel variants may be present that could lead to false-negative or false-positive results. There may be rare or novel HLA-B alleles that could interfere with this assay. There are, as yet, no data indicating whether any other allele or subtypes are associated with abacavir hypersensitivity or pazopanib hepatotoxicity.

Supportive Data

Sensitivity of this assay for detecting the human leukocyte antigen HLA-B*57:01 allele approaches 100% with specificity near 96%.(3)

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Xu CF, Johnson T, Wang X, et al: HLA-B*57:01 confers susceptibility to pazopanib-associated liver injury in patients with cancer. Clin Cancer Res. 2016;22(6):1371-1377

2. Pazopanib. Package insert. Novartis Pharmaceuticals; Updated August 2020. Accessed March 22, 2021. Available at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eeaaaf38-fb86-4d9f-a19d-0f61daac2fd7

3. Saag M, Balu R, Brachman P, et al: High sensitivity of HLA-B*5701 in whites and blacks in immunologically-confirmed cases of abacavir hypersensitivity. Fourth IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract WEAB305

4. Martin M, Klein T, Dong B, Pirmohamed M, Haas DW, Kroetz DL: Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B genotype and abacavir dosing. Clin Pharmacol Ther. 2012;91(4):734-738

5. Martin M, Hoffman J, Freimuth R, et al: Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B genotype and abacavir dosing: 2014 update. Clin Pharmacol Ther. 2014;95(5):499-500

6. Faruki H, Heine U, Brown T, Koester R, Lai-Goldman M: HLA-B*5701 clinical testing: early experience in the United States. Pharmacogenet Genomics. 2007;17:857-860

7. Sun HY, Hung CC, Lin PH, et al: Incidence of abacavir hypersensitivity and its relationship with HLA-B*5701 in HIV-infected patients in Taiwan. J Antimicrob Chemother. 2007;60:599-604

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Genomic DNA is extracted from the sample. Amplification for the HLA-B*57:01 allele and an internal control gene is performed by real-time polymerase chain reaction (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.(Hammond E, Mamotte C, Nolan D, Mallal S: HLA-B*5701 typing: evaluation of an allele-specific polymerase chain reaction melting assay. Tissue Antigens. 2007 Jul;70[1]:58-61)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood/Saliva: 2 weeks; Extracted DNA: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) 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 US 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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81381

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports