Detection of HLA-B*58:01, the susceptible allele for allopurinol-induced hypersensitivity, by loop-mediated isothermal amplification

Br J Dermatol. 2013 Mar;168(3):526-32. doi: 10.1111/bjd.12097.

Abstract

Background: Allopurinol, a common medication for gout treatment, can cause rare but life-threatening severe cutaneous adverse reactions. A strong pharmacogenetic association of human leucocyte antigen (HLA)-B*58:01 with allopurinol-induced drug hypersensitivity has been reported, especially in the Han Chinese population.

Objectives: To develop a rapid and simple loop-mediated isothermal amplification (LAMP) assay of HLA-B*58:01 and evaluate its feasibility in predicting allopurinol-induced drug hypersensitivity.

Methods: Two sets of LAMP primers targeting exons 2 and 3 of HLA-B*58:01 were designed. DNA extracted from 20 clinical blood samples of patients with gout was used to evaluate the effectiveness of the two LAMP primer sets for the detection of HLA-B*58:01.

Results: The results were compared with routine clinical genotyping methods. All extracted DNA samples tested with the HLA-B*58:01 LAMP assay showed agreement with the routine genotyping results. No amplifications were observed when unextracted blood samples were tested.

Conclusions: The HLA-B*58:01 LAMP assay was confirmed to be simple, rapid and specific for the detection of HLA-B*58:01, and therefore of potential value in the diagnosis of allopurinol-induced hypersensitivity.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / adverse effects*
  • Cost-Benefit Analysis
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / economics
  • Drug Hypersensitivity / genetics
  • Feasibility Studies
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Gout Suppressants / adverse effects*
  • HLA-B Antigens / genetics*
  • Humans
  • Nucleic Acid Amplification Techniques / economics
  • Nucleic Acid Amplification Techniques / methods*
  • Nucleic Acid Amplification Techniques / standards
  • Sensitivity and Specificity

Substances

  • Gout Suppressants
  • HLA-B Antigens
  • HLA-B58 antigen
  • Allopurinol