Genome-Wide Association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe by Genin Emmanuelle, Schumacher Martin, Roujeau Jean-Claude, Naldi Luigi, Liss Yvonne, Kazma Remi, Sekula Peggy, Hovnanian Alain, Mockenhaupt Maja in Orphanet journal of rare diseases (2011).

[PMID: 21801394] PubMed


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. 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 (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. 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.

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