title: Genome-wide association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Inserm U, Paris, France. emmanuelle.genin@inserm.fr
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Génin
authors.forename: Martin
authors.initials: M
authors.lastname: Schumacher
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Roujeau
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldi
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Liss
authors.forename: Rémi
authors.initials: R
authors.lastname: Kazma
authors.forename: Peggy
authors.initials: P
authors.lastname: Sekula
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
authors.forename: Maja
authors.initials: M
authors.lastname: Mockenhaupt
mesh_terms: D000493:Allopurinol / Q000009:adverse effects*; D016022:Case-Control Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D005060:Europe; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D013262:Stevens-Johnson Syndrome / Q000209:etiology / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; C500126:HLA-B*58:01 antigen; D000493:Allopurinol