Simple and rapid detection of HLA-A*31:01 for prediction of carbamazepine-induced hypersensitivity using loop-mediated isothermal amplification method

J Dermatol Sci. 2014 Apr;74(1):88-92. doi: 10.1016/j.jdermsci.2013.11.013. Epub 2013 Dec 16.

Abstract

Background: Carbamazepine (CBZ), which is widely used in management of epilepsy or neuropathic pain, causes fatal severe cutaneous adverse reactions (SCARs). CBZ-induced SCARs are known to occur in strong association with human leukocyte antigen (HLA)-A*31:01 in Japanese and European populations. HLA genotyping is currently used to detect human HLA-A*31:01.

Objective: To establish a simple and rapid screening assay specific for HLA-A*31:01, the loop-mediated isothermal amplification (LAMP) method was employed on a sample Japanese population.

Methods: A set of LAMP primers targeting exon 2 of HLA-A*31:01 were designed. Thirty-two clinical samples including the representative HLA-A allele in Japan were used to assess the specificity of LAMP primers in the detection of HLA-A*31:01.

Results: The HLA-A*31:01-specific LAMP assay showed consistency with polymerase chain reaction reverse sequence-specific oligonucleotide probe (PCR-rSSO) and polymerase chain reaction-sequence based typing (PCR-SBT) results.

Conclusion: High sensitivity and specificity of the HLA-A*31:01 LAMP assay was confirmed. Considering its convenience, the assay can be widely used to screen patients at high genetic risk of CBZ-induced SCARs.

Keywords: Carbamazepine; Fatal severe cutaneous adverse reactions; Human leukocyte antigen-A*31:01; Loop-mediated isothermal amplification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Anticonvulsants / adverse effects
  • Base Sequence
  • Carbamazepine / adverse effects*
  • DNA Primers / genetics
  • Drug Hypersensitivity / genetics*
  • Drug Hypersensitivity / mortality
  • Gene Frequency
  • Genotype
  • HLA-A Antigens / analysis*
  • Humans
  • Japan
  • Molecular Sequence Data
  • Nucleic Acid Amplification Techniques*
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Skin / drug effects

Substances

  • Anticonvulsants
  • DNA Primers
  • HLA-A Antigens
  • HLA-A*31:01 antigen
  • Carbamazepine