Genetic markers associated with cutaneous adverse drug reactions to allopurinol: a systematic review

Pharmacogenomics. 2015;16(7):755-67. doi: 10.2217/pgs.15.21. Epub 2015 May 12.


Pharmacogenomic markers in the HLA coding genes have been associated with drug hypersensitivity of multiple drugs, including allopurinol. In this systematic review, we summarize the pharmacogenomic evidence available regarding allopurinol-induced cutaneous adverse drug reactions (cADRs). We found that the HLA-B*5801 allele was significantly associated with the risk of severe cADRs in the Han Chinese, Korean, Thai, Japanese and European populations. The association between less severe cADRs and HLA-B*5801 was less consistent. All SNPs identified in genome-wide association studies of common variants were also located in or nearby HLA-B*5801. Future studies should focus on more common but less severe allopurinol-induced cADRs, as well as the potential role of rare variants as predictors of these cADRs.

Keywords: HLA; Stevens–Johnson syndrome; adverse reaction; allopurinol; drug-induced hypersensitivity syndrome; pharmacogenomics; rash; safety; toxic epidermal necrolysis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Allopurinol / adverse effects*
  • Drug Eruptions / diagnosis*
  • Drug Eruptions / genetics*
  • Drug-Related Side Effects and Adverse Reactions / diagnosis
  • Drug-Related Side Effects and Adverse Reactions / genetics
  • Genetic Markers / drug effects
  • Genetic Markers / genetics*
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / trends
  • HLA Antigens / genetics
  • Humans
  • Pharmacogenetics / methods
  • Pharmacogenetics / trends
  • Polymorphism, Single Nucleotide / genetics


  • Genetic Markers
  • HLA Antigens
  • Allopurinol