Prediction of individual difference via a side effect mechanism

<p>Understanding individual differences, such as age and gender, is important to consider personalized medicine. Human iPS cells are expected to be used to understand individual differences. Previous studies reported that patient-derived iPS cells can predict responders and non-responders. Using a large-scale G-protein-coupled receptor screening and human iPS cell-based assays, we found that the COVID-19 drug remdesivir mediated urotensin-II receptor activation and resulted in drug-mediated cardiotoxicity. To understand the impact of genetic variance on the susceptibility to remdesivir–urotensin-II receptor signaling in humans, we analyzed single-nucleotide variant information from a large-scale genomic database from 14,000 Japanese individuals. We found that there are more than 2,000 variants in the urotensin-II receptor and 110 missense mutations involving a single amino acid substitution. In addition, we identified the mutation in the urotensin-II receptor gene are sensitive to remdesivir, which may possibly be more susceptible to urotensin-II receptor-mediated cardiotoxicity. These approach may be able to predict adverse drug responses in humans. </p><p>In the future, the development of a cell bank using patient-derived iPS cells would facilitate research on individual differences.</p>