Scandinavian journal of clinical and laboratory investigation

Carbamazepine-induced cutaneous reactions: a simple assay to identify patients carrying the HLA-A*31:01 allele.

PMID 24882392


Treatment with the first-line antiepileptic drug, carbamazepine (CBZ), is associated with adverse cutaneous reactions in up to 10% of patients. One predisposition to these side-effects has been linked to the HLA-A*31:01 allele. HLA-typing is costly and time-consuming. A single nucleotide polymorphism (SNP, rs1061235A > T) has been suggested as a marker for the HLA-A*31:01 allele. We sought to develop and validate a simple, fast and inexpensive assay for rs1061235 to apply in the Norwegian population. We designed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for the SNP and tested it on a set of 16 samples with known HLA-A alleles. The assay identified all HLA-A*31:01 alleles present, but also marked for HLA-A*33:03. In a second set of 204 samples from Norwegian epilepsy patients with unknown HLA alleles, nine samples heterozygous for the rs1061235 were found. Subsequent HLA-typing showed that one sample was HLA-A*33:01, whereas the other eight were identified as HLA-A*31:01. The remaining 195 samples were correctly identified as neither carrying the rs1061235 SNP nor HLA-A*31:01. The sensitivity and specificity of the rs1061235 SNP test was 100% and 99.5%, respectively. Misinterpretation of the rare HLA-A*33 variants as HLA-A*31:01 has minor consequence, as it only would result in choosing an alternative drug to CBZ. We have designed and validated a simple, fast and inexpensive test for the rs1061235A> T SNP as a marker for HLA-A*31:01 in the Norwegian population for potential use in a personalized treatment approach to patients planned to receive CBZ.