Events

31 Oct 2012

16:30

Lecture Theatre 6, Lee Shau Kee Building, CUHK

Professor Chen, Yuan-Tsong

Professor Chen is currently a Distinguished Research Fellow and former director of the Institute of Biomedical Sciences, Academia Sinica, Taiwan, and he also holds chair Professor of Pediatrics at Duke University Medical Center in USA.

Free

3943 7598/ 3943 7455
Seat reserve please email to amyyeung@cuhk.edu.hk for enrollment

Clinically observed drug toxicity so called adverse drug reactions (ADRs) account for 6-7 % of all hospital admissions and remain a major clinical problem. Pharmacogenomics aims to investigate the genetic basis of inter-individual differences in drug responses, such as efficacy, dose requirements, and adverse events. Research in pharmacogenomics has grown over the past decade, evolving from a candidate-gene approach to genome-wide association studies (GWAS). Genetic variants in genes coding for drug metabolism, drug transport, and more recently human-leukocyte antigens (HLA) have been linked to inter-individual differences in the risk of adverse drug reactions. I will use the following as an example to show that personalized medicine and pharmacogenomics is extremely useful in the right clinical settings.
Stevens-Johnson syndrome (SJS) and the related disease, toxic epidermal necrolysis (TEN), are two of the most serious ADRs. Carbamazepine (CBZ), used primarily in the treatment of epilepsy, neuralgia and bipolar disorder, is the commonest cause of SJS/TEN in Southeast Asian countries. We previously reported that CBZ-induced SJS/TEN in Chinese and many Southeast Asian populations are strongly associated with the human leukocyte antigen (HLA) B*1502. The strong genetic association suggests a direct involvement of HLA in the pathogenesis of drug hypersensitivity and indeed HLA molecule presents an antigenic drug and resulted in clonal expansion and activation of CD8+ cytotoxic T cells have been shown. Pharmacogenomic study also identified an unusual form of granulysin secreted by these cytotoxic T lymphocytes and natural killer cells responsible for the rapid and disseminated keratinocyte death in SJS/TEN. The high sensitivity/specificity of genetic markers provides a plausible basis for developing tests to identify individuals at risk for drug hypersensitivity and indeed a large prospective study has shown that HLA-B*1502 screening before carbamazepine treatment can effectively reduce the incidence of CBZ-induced SJS/TEN. These translational researches demonstrated that preventing drug toxicity by screening people at risk before prescription of a drug is a clinical reality. Application of HLA-B*1502 genotyping as a screening tool for patient taking carbamazepine is now recommended by the Department of Health, Taiwan and by the US FDA.

Lecture delivered in English