The impact of , , and polymorphisms on tacrolimus dose-adjusted concentration and clinical outcomes in adult allogeneic hematopoietic stem cell transplantation.

1. Polymorphisms in genes related to drug-metabolizing genes may affect tacrolimus exposure. This study aimed to assess the influence of , , and polymorphisms on tacrolimus pharmacokinetics and outcomes in allogeneic hematopoietic stem cell transplantation (HSCT).2. 46 adult patients receiving oral tacrolimus at an initial dose of 0.03mg/kg/day for acute graft versus host disease (GVHD) prophylaxis after allogeneic HSCT were enrolled in this retrospective study. Genetic polymorphisms were detected in relation to concentration/dose (C/D) ratios of tacrolimus and the incidence of acute GVHD and acute kidney injury (AKI).3. The genotype and co-administration of voriconazole were significantly associated with increased C/D ratios of tacrolimus ( < 0.05). 8055CC present a significant higher tacrolimus C/D ratio compared with carriers of 8055CT and 8055TT genotypes in allogeneic HSCT recipients with the allele ( = 0.033). Younger age and recipients with the allele were significantly associated with higher incidence of II-IV acute GVHD post-transplantation.4. , 8055 C > T, and concomitant use of voriconazole are important determinants affecting tacrolimus pharmacokinetics. Moreover, allele and younger age are independent risk factors for II-IV acute GVHD in HSCT recipients.