Association of Hepatic Nuclear Factor 4 Alpha Gene Polymorphisms With Free Imatinib Plasma Levels and Adverse Reactions in Chinese Gastrointestinal Stromal Tumor Patients

摘要

Background: As the first-line treatment of gastrointestinal stromal tumor (GIST), the pharmacokinetic and pharmacodynamic of imatinib (IM) were characterized by marked interindividual variability. Pharmacogenetics of IM involved metabolic enzymes and transporters have been extensively reported, but the results remained inconsistent. This study investigated the effect of genetic variants in hepatocyte nuclear factor 4 alpha (HNF4 alpha, encoded by gene NR2A1), a pivotal transcriptional regulator of drug disposition genes, on dose-adjusted IM-free plasma levels and related adverse reactions in Chinese GIST patients.