Steitz, Alyssa; Daniel, Laura L.; Nepal, Puran; Dickson, Alyson L.; Zanussi, Jacy; Miller-Fleming, Tyne W.; Straub, Peter S.; Wei, Wei-Qi; Liu, Ge; Maizel, Jennifer; Cox, Nancy J.; Hung, Adriana M.; Feng, QiPing; Stein, C. Michael; Chung, Cecilia P. (2026).听.听BMC Pharmacology and Toxicology, 27(1), 89.听
Some people experience serious side effects from聽azathioprine, a medication commonly used to treat autoimmune diseases, and genetic differences can influence that risk. While variants in the聽TPMT听补苍诲听NUDT15聽genes are already known to increase the likelihood of聽myelotoxicity聽(damage to the bone marrow that can reduce blood cell production), other genetic factors remain less well understood. In this study, the researchers used聽PrediXcan, a computational method that estimates how strongly a person’s genes are likely to be expressed based on their genetic data, to investigate whether predicted gene expression was associated with known azathioprine side effects. They analyzed data from 1,364 people who had recently started azathioprine and found that individuals with the lowest predicted expression of the聽TPMT聽gene had more than three times the odds of developing聽leukopenia聽(a low white blood cell count) compared with those with the highest predicted TPMT expression. No significant associations were found for other known side effects. These findings suggest that approaches such as PrediXcan may help identify additional genetic factors that influence how people respond to medications, supporting more personalized treatment in the future.
Fig 1
Predicted expression of聽TPMT聽in liver tissue by聽TPMT聽phenotype group