Genetic Architecture of DILI in the Polygenic Risk Score Era-Genetic Architecture of DILI

Video Transcription

Video Summary

The video is a detailed seminar featuring Dr. Paola Nicoletti, a leading expert in pharmacogenetics and the genomics of drug-induced liver injury (DILI). The discussion centers around the genetic susceptibility to DILI, a rare but severe adverse drug reaction affecting the liver. Dr. Nicoletti highlights key challenges in studying DILI genetics, such as the rarity of cases requiring collaboration and standardized phenotyping. She presents findings that multiple HLA alleles and other immune-related genes, including PTPN22 and ERAP2, contribute to DILI risk, sometimes in drug-specific ways. Importantly, she introduces the concept of polygenic risk scores (PRS) for DILI, which aggregate the effect of multiple genetic variants to estimate individual risk, showing promise for clinical application, especially for drugs like amoxicillin-clavulanate. The seminar also touches on the limited role of pharmacogenes (PGX genes) in DILI susceptibility, except in specific cases like NAT2 with anti-TB drug reactions. Attendees engage in a Q&A discussing potential future applications of PRS in clinical practice and drug development, challenges in turnaround time, insurance coverage, and the feasibility of preemptive genetic testing. Overall, the session underscores the potential for genetics to improve DILI diagnosis, risk stratification, and understanding of liver disease biology, while acknowledging the need for further research to validate genetic risk scores and integrate them into clinical decision-making. The talk emphasizes collaboration and ongoing efforts to refine predictive tools for safer personalized medicine in hepatology.

Keywords

pharmacogenetics

drug-induced liver injury

DILI genetics

HLA alleles

immune-related genes

PTPN22

ERAP2

polygenic risk scores

amoxicillin-clavulanate

NAT2 gene

personalized medicine