A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients

Pharmacogenomics J. 2013 Feb;13(1):60-9. doi: 10.1038/tpj.2011.41. Epub 2011 Sep 13.


Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10(-8); odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Allopurinol / adverse effects*
  • Allopurinol / therapeutic use
  • Asian People / genetics
  • Biomarkers / metabolism
  • Chromosomes, Human, Pair 6 / drug effects
  • Chromosomes, Human, Pair 6 / genetics
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Genome-Wide Association Study / methods
  • HLA Antigens / genetics
  • HLA Antigens / metabolism
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Stevens-Johnson Syndrome / chemically induced
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*
  • Stevens-Johnson Syndrome / metabolism


  • Biomarkers
  • HLA Antigens
  • Allopurinol