Effect of and polymorphisms on the valproic acid serum concentration and drug-induced liver injury.

Valproic acid (VPA) is a classic broad-spectrum antiepileptic drug, with significant pharmacokinetic variability. Genetic polymorphisms contribute to this variability, influencing both VPA trough serum concentration (VPA concentration) and VPA-induced liver injury. Our study aims to investigate the association between polymorphisms of uridine diphosphate glucuronyl transferase () , and VPA concentration and screen for potential genetic loci affecting VPA-induced liver injury. This study included epilepsy patients treated with VPA. PCR-RFLP method was used to determine the genotypes of and . Chemiluminescent microparticle immunoassay was used to measure VPA concentration. Multiple linear regression and logistic regression were employed to analyze factors influencing VPA concentration and VPA-induced liver injury, respectively. The correlation between polymorphism and VPA concentration was analyzed in 133 samples. For VPA-induced liver injury, 105 patients were analyzed, with 29 in the liver injury group and 76 in the control group. Our finding showed patients with the variant had significantly lower VPA concentrations compared with wild-type patients and polymorphisms showed no impact on VPA-induced liver injury. This study demonstrated polymorphisms affected the VPA concentration, providing a theoretical basis for the individualized clinical use of VPA.