Test directory: HLA-B*58:01 Genotyping

Ordering Code 7931
Test Name HLA-B*58:01 Genotyping
Alias HLA-B*58:01 Genotyping, Allopurinol Hypersensitivity
HLA-B*58:01
Preferred Specimen Whole Blood
Preferred Container EDTA, K2 (Lavender)
Other Specimen/Container Whole Blood in ACD-B (Yellow)
Optimum Volume 5 mL
Transport Requirements Oahu: Ambient
Airline: Refrigerated
Specimen Stability Ambient: 3 Days
Refrigerated: 1 Week
Frozen: Not Stable
Rejection Criteria Frozen, Heparinized
Avail. Stat NO
Analytic Time 7 Days
Methodology Polymerase Chain Reaction/Sequence-Specific Oligonucleotide
Probe Hybridization
Reference Lab  ARUP Laboratories

Reference range(s)

The reference ranges listed below are valid on this date of June 29, 2025.
Component Age Male Norm Male Critical Low Male Critical High Female Norm Female Critical High Female Critical Low Units Add'l info
HLA-B*58:01 Genotyping ALL

BACKGROUND...
BACKGROUND INFORMATION CHARACTERISTICS:
Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. It inhibits xanthine oxidase, a key enzyme involved in uric acid formation. However, allopurinol is one of the most common causes of life-threatening severe cutaneous adverse reactions (SCAR), which include drug hypersensitivity syndrome, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The presence of HLA-B*58:01 allele shows strong association with allopurinol-induced SCAR, including
TEN and SJS. Although allopurinol-induced SCAR is rare with an estimated risk of 0.1-0.4 percent in allopurinol users, the severity can be high, with a mortality rate of up to 25 percent. Symptoms include rash, combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Due to the severity of adverse reactions, it is recommended to test for the HLA-B*58:01 allele prior to initiation of the drug

INCIDENCE: HLA-B*58:01 allele frequency varies by ethnicity. In the US population, the highest incidence at 5.3 percent is found in Asians, 3.8 percent in African Americans, 1.45 percent in Native
Hawaiians or Pacific Islanders, 1.35 percent in
Hispanics, 1.19 percent in American Indians or
Alaska Natives and 0.8 percent in Caucasians
Frequencies may be higher in other countries, up to 20 percent in Singapore, Taiwan and among Han
Chinese, 15.4 percent in India, 14.2 percent in Hong
Kong, 12 percent in China and Korea, 11 percent in
Indonesia

CAUSE: Allopurinol-induced SCAR, including SJS and
TEN, is strongly associated with the presence of one or two copies of HLA-B*58:01 allele. The mechanism is immune mediated and involves direct interactions between the allopurine metabolite oxypurinol, and
HLA-B*58:01, which may result in drug-induced changes in peptide presentation, allowing activation of self-reactive T lymphocytes

ALLELES TESTED: HLA-B*58:01 allele

CLINICAL SENSITIVITY AND SPECIFICITY: 71 percent sensitivity and 92 percent specificity, overall mean values from pooled populations (Yu KH et al, Int J Rheum Dis 2017). Higher in populations with increased HLA-B*58:01 allele frequency

METHODOLOGY: PCR followed by Sequence Specific
Oligonucleotide Probe Hybridization of HLA-B locus

ANALYTICAL SENSITIVITY AND SPECIFICITY:
Greater than 99 percent

LIMITATIONS: Copy number of HLA-B*58:01 will not be reported. Other genetic and non-genetic factors that influence allopurinol hypersensitivity are not evaluated. Other rare, or novel alleles may occur which may lead to false positive or false negative results

Test systems were developed and their performance characteristics determined by the H&I laboratory at the University of Utah Health, under the accreditation guidelines from the American Society for Histocompatibility and Immunogenetics (ASHI)

See report.
Note1

Note1:


BACKGROUND INFORMATION CHARACTERISTICS:
Allopurinol is the most commonly used drug for the treatment of hyperuricemia and gout. It inhibits xanthine oxidase, a key enzyme involved in uric acid formation. However, allopurinol is one of the most common causes of life-threatening severe cutaneous adverse reactions (SCAR), which include drug hypersensitivity syndrome, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The presence of HLA-B*58:01 allele shows strong association with allopurinol-induced SCAR, including
TEN and SJS. Although allopurinol-induced SCAR is rare with an estimated risk of 0.1-0.4 percent in allopurinol users, the severity can be high, with a mortality rate of up to 25 percent. Symptoms include rash, combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Due to the severity of adverse reactions, it is recommended to test for the HLA-B*58:01 allele prior to initiation of the drug

INCIDENCE: HLA-B*58:01 allele frequency varies by ethnicity. In the US population, the highest incidence at 5.3 percent is found in Asians, 3.8 percent in African Americans, 1.45 percent in Native
Hawaiians or Pacific Islanders, 1.35 percent in
Hispanics, 1.19 percent in American Indians or
Alaska Natives and 0.8 percent in Caucasians
Frequencies may be higher in other countries, up to 20 percent in Singapore, Taiwan and among Han
Chinese, 15.4 percent in India, 14.2 percent in Hong
Kong, 12 percent in China and Korea, 11 percent in
Indonesia

CAUSE: Allopurinol-induced SCAR, including SJS and
TEN, is strongly associated with the presence of one or two copies of HLA-B*58:01 allele. The mechanism is immune mediated and involves direct interactions between the allopurine metabolite oxypurinol, and
HLA-B*58:01, which may result in drug-induced changes in peptide presentation, allowing activation of self-reactive T lymphocytes

ALLELES TESTED: HLA-B*58:01 allele

CLINICAL SENSITIVITY AND SPECIFICITY: 71 percent sensitivity and 92 percent specificity, overall mean values from pooled populations (Yu KH et al, Int J Rheum Dis 2017). Higher in populations with increased HLA-B*58:01 allele frequency

METHODOLOGY: PCR followed by Sequence Specific
Oligonucleotide Probe Hybridization of HLA-B locus

ANALYTICAL SENSITIVITY AND SPECIFICITY:
Greater than 99 percent

LIMITATIONS: Copy number of HLA-B*58:01 will not be reported. Other genetic and non-genetic factors that influence allopurinol hypersensitivity are not evaluated. Other rare, or novel alleles may occur which may lead to false positive or false negative results

Test systems were developed and their performance characteristics determined by the H&I laboratory at the University of Utah Health, under the accreditation guidelines from the American Society for Histocompatibility and Immunogenetics (ASHI)

See report..