Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Serious adverse drug reactions (SADRs), such as severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI), are often caused by idiosyncratic drug reactions influenced by the patient's genetic factors. The association between carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and human leukocyte antigen (HLA)-B*15:02 in Han Chinese is a well-known example. The prevalence of genetic risk factors varies greatly among ethnicities. Therefore, associations found in other ethnicities are not necessarily reproducible in Japanese population. For example, our group has previously found that HLA-B*15:11, but not HLA-B*15:02, is associated with carbamazepine-SJS/TEN in Japanese patients. This indicates that identifying risk factors for idiosyncratic SADRs requires case collection and association analysis specific to each ethnicity.
Since 2009, the National Institute of Health Sciences has been conducting a research project to identify genomic biomarkers associated with SADR development, in response to the "Predictive and Preventive Safety Measures" of the Ministry of Health, Labour and Welfare. We have collected cases of SJS/TEN, DILI, drug-induced interstitial lung diseases, and rhabdomyolysis. We used the genome data of healthy Japanese individuals collected by the Japan PGx Data Science Consortium as a control, and identified genomic biomarkers associated with the development of SADRs caused by various drugs.
Furthermore, our group has identified the association of HLA-A*11:01 with SCARs caused by sulfonamides and the association of HLA-B*35:01 with DILI caused by Kampo medicines. In addition to these results, we will also present the pathomechanisms of HLA-mediated SADRs.
