Sign in →

Test ID: HL57R HLA-B*57:01 Genotype, Pharmacogenomics, Varies


Specimen Required


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


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.

Useful For

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

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.

Method Name

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

Reporting Name

HLA-B 5701 Genotype, V

Specimen Type

Varies

Specimen Minimum Volume

Blood: 0.4 mL
Saliva: 1 swab

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

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

Negative

An interpretive report will be provided.

Interpretation

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.

Clinical Reference

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

Day(s) Performed

Monday, Wednesday through Friday

Report Available

1 to 5 days

Test Classification

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

81381

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HL57R HLA-B 5701 Genotype, V 50956-2

 

Result ID Test Result Name Result LOINC Value
610672 HLA-B *57:01 Genotype 50956-2
610673 HLA-B *57:01 Phenotype 93308-5
610674 Interpretation 69047-9
610675 Additional Information 48767-8
610676 Method 85069-3
610677 Disclaimer 62364-5
610678 Reviewed by 18771-6
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-pgx