title: Carbamazepine-induced cutaneous reactions: a simple assay to identify patients carrying the HLA-A*31:01 allele.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Biochemistry, St Olavs Hospital , Trondheim , Norway.
authors.forename: Ketil
authors.initials: K
authors.lastname: Thorstensen
authors.forename: Mona
authors.initials: M
authors.lastname: Kvitland
authors.forename: Maryam
authors.initials: M
authors.lastname: Shirzadi
authors.forename: Grethe
authors.initials: G
authors.lastname: Helde
authors.forename: Torolf
authors.initials: T
authors.lastname: Moen
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: D000927:Anticonvulsants; D005819:Genetic Markers; D015234:HLA-A Antigens; D002220:Carbamazepine
keywords: Adverse cutaneous reactions; CBZ; Marker; Single nucleotide polymorphism