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HLA-B genotyping to detect carbamazepine-induced Stevens-Johnson syndrome: implications for personalizing medicine.

Research paper by Shuen-Iu SI Hung, Wen-Hung WH Chung, Yuan-Tsong YT Chen

Indexed on: 01 Aug '05Published on: 01 Aug '05Published in: Personalized medicine



Abstract

Preventing severe adverse drug reactions by identifying people at risk with a simple genetic test is the goal of many pharmacogenomic studies. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are related, life-threatening cutaneous adverse reactions, most often caused by medication. The overall incidence and the commonly offending drugs vary among different ethnic populations. Susceptibility to such idiosyncratic reactions is thought to be genetically determined and immune mediated. Finding a strong genetic association between a particular human leukocyte antigen (HLA)-B allele and the reaction to a specific drug provides evidence that the pathogenesis of the severe cutaneous adverse drug reactions involves major histocompatibility complex-restricted presentation of a drug or its metabolites for T-cell activation. In the case of carbamazepine-induced SJS/TEN, the tight association of the HLA-B*1502 allele (sensitivity 100%, specificity 97% and odds ratio 2504) provides a plausible basis for further development of such a test to identify individuals at risk of developing this life-threatening condition.