HLA-B 1502 Genotype, Carbamazepine Hypersensitivity, Blood
Identifying individuals of Asian ancestry who are at risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis when administered carbamazepine, phenytoin, or fosphenytoin therapy
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Clinical studies have demonstrated associations between some human leukocyte antigen (HLA) genotypes and drug-induced adverse skin reactions. The presence of the HLA-B*1502 allele increases the risk of developing toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS), a milder form of TEN. The frequency of the HLA-B*1502 allele varies throughout Asia: 10% to 15% frequency in Chinese, 2% to 4% frequency in Southeast Asians, including Indians, and <1% frequency in Japanese and Koreans.
The FDA recommends that individuals of Asian ancestry be genotyped for the presence of the HLA-B*1502 allele prior to receiving:
-Carbamazepine, a drug used to treat epilepsy, manic/bipolar disorders, and neuropathic pain
-Phenytoin and its soluble precursor fosphenytoin, drugs used to control seizures
Some studies have also suggested a connection between HLA-B*1502 positivity and adverse reactions to lamotrigine used for treating epilepsy and bipolar disorder.
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.
Positivity for HLAB*1502 confers increased risk for hypersensitivity to carbamazepine, phenytoin, or fosphenytoin
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Patients who have received a heterologous blood transfusion within the preceding 6 weeks, or who have received an allogeneic blood or marrow transplant, can have inaccurate genetic test results due to presence of donor DNA.
This test may give false-positive results for individuals who carry certain HLA-B alleles (eg, *1513, *1531, *1555, *1588, *1589, *1820, *9512, *9521, *9544, and *9570). However, most of these alleles are rare and exist in only specific ethnicities. For example, HLAB*1513, while rare, has been observed more in Asian populations than other populations. Thus, the false positive rate of this test depends on the frequency of this HLA-B allele in individual patient’s ethnic group. In addition, other rare, undocumented alleles may occur and may or may not affect the results of this assay. There are no data indicating whether these subtypes are associated with hypersensitivity. If results obtained do not match the clinical findings, additional testing should be considered.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Man CB, Kwan P, Baum L, et al: Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 2007;40:1015-1018
2. Chung WH, Hung SL, Hong HS, et al: Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428:486
3. Hung SL, Chung WH, Jee SH, et al: Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reaction. Pharmacogenet Genomics 2006;16:297-306
4. Cox ST, McWhinnie AJ, Robinson J, et al: Cloning and sequencing full-length HLA-B and -C genes. Tissue Antigens 2003;61:20-48
5. Hung, Shuen-Iu. Chung, Wen-Hung. Liu, Zhi-Sheng. Chen et al: Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11:349-356