Abstract
BackgroundStevens-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.ObjectivesTo investigate genetic association at a genome-wide level on a large sample of SJS/TEN patients.MethodsWe performed a genome wide association study on a sample of 424 European cases and 1,881 controls selected from a Reference Control Panel.ResultsSix 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 (ORallopurinol = 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.ConclusionThe 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.
Highlights
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
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 the largest one collected so far
If some loci outside HLA play a role in SJS/TEN, their effect is likely to be very small
Summary
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. SJS and TEN are severe cutaneous adverse reactions characterized by the development of acute exanthema which progresses towards limited (in SJS) or widespread (in TEN) blistering and erosion of the skin and mucous membranes [4]. The incidence of SJS/TEN is estimated to be of approximately 1-2 patients per million individuals per year [6]. It is a very rare disease but SJS/TEN is not associated with a single drug or a single group of drugs but several different drugs have been involved. A small number of individuals exposed to these “highly suspected” drugs develop the disease and a genetic susceptibility has been suggested [9,10,11,12]
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