Genome-wide association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe

Orphanet J Rare Dis. 2011 Jul 29;6:52. doi: 10.1186/1750-1172-6-52.


Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare but extremely severe cutaneous adverse drug reactions in which drug-specific associations with HLA-B alleles were described.

Objectives: To investigate genetic association at a genome-wide level on a large sample of SJS/TEN patients.

Methods: We performed a genome wide association study on a sample of 424 European cases and 1,881 controls selected from a Reference Control Panel.

Results: Six SNPs located in the HLA region showed significant evidence for association (OR range: 1.53-1.74). The haplotype formed by their risk allele was more associated with the disease than any of the single SNPs and was even much stronger in patients exposed to allopurinol (OR(allopurinol) = 7.77, 95%CI = [4.66; 12.98]). The associated haplotype is in linkage disequilibrium with the HLA-B*5801 allele known to be associated with allopurinol induced SJS/TEN in Asian populations.

Conclusion: The involvement of genetic variants located in the HLA region in SJS/TEN is confirmed in European samples, but no other locus reaches genome-wide statistical significance in this sample that is also the largest one collected so far. If some loci outside HLA play a role in SJS/TEN, their effect is thus likely to be very small.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / adverse effects*
  • Case-Control Studies
  • Drug-Related Side Effects and Adverse Reactions
  • Europe
  • Female
  • Gene Frequency
  • Genome-Wide Association Study*
  • HLA-B Antigens / genetics*
  • Humans
  • Male
  • Odds Ratio
  • Stevens-Johnson Syndrome / etiology
  • Stevens-Johnson Syndrome / genetics*
  • White People / genetics*


  • HLA-B Antigens
  • HLA-B*58:01 antigen
  • Allopurinol