Development of a rapid and inexpensive assay for detecting a surrogate genetic polymorphism of HLA-B*58:01: a partially predictive but useful biomarker for allopurinol-related Stevens-Johnson syndrome/toxic epidermal necrolysis in Japanese

Drug Metab Pharmacokinet. 2012;27(4):447-50. doi: 10.2133/dmpk.dmpk-11-nt-120. Epub 2012 Jan 24.

Abstract

Allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is strongly associated with HLA-B*58:01 in various populations including Japanese. We demonstrated that several single nucleotide polymorphisms (SNPs) around the HLA region on chromosome 6 were strongly linked with HLA-B*58:01 in a previous study using Japanese allopurinol-related SJS/TEN patients. Their very strong linkage suggests that these SNPs could be used as surrogate biomarkers to find carriers of HLA-B*58:01 to avoid these serious adverse effects. In the present study, to expedite the application of this pharmacogenomic information to the proper usage of allopurinol in a clinical situation, we developed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for the genotyping of rs9263726 in the psoriasis susceptibility 1 candidate 1 (PSORS1C1) gene, which is in absolute linkage disequilibrium (r(2) = 1, D' = 1) with HLA-B*58:01. The developed PCR-RFLP assay using FokI restriction enzyme was able to detect three different genotypes, GG, GA, and AA of rs9263726 robustly, and thus to find HLA-B*58:01 carriers. This robust and inexpensive assay would be useful for pre-screening the subjects with HLA-B*58:01, a genetically high risk factor for allopurinol-induced SJS/TEN.

Publication types

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

MeSH terms

  • Allopurinol / adverse effects*
  • Amplified Fragment Length Polymorphism Analysis
  • Asian People / genetics*
  • Gene Frequency
  • Genetic Markers
  • Genetic Predisposition to Disease
  • HLA-B Antigens / genetics*
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Japan
  • Linkage Disequilibrium
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Proteins / genetics*
  • Risk Assessment
  • Risk Factors
  • Stevens-Johnson Syndrome / chemically induced
  • Stevens-Johnson Syndrome / ethnology
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*
  • Stevens-Johnson Syndrome / immunology

Substances

  • Genetic Markers
  • HLA-B Antigens
  • HLA-B*58:01 antigen
  • PSORS1C1 protein, human
  • Proteins
  • Allopurinol