Association Between CYP3A5*3 Polymorphism and Graft-versus-host Disease in Allogeneic Hematopoietic Stem Cell Transplant Patients Receiving Tacrolimus

Tacrolimus is a prophylactic for graft-versus-host disease (GVHD), a major cause of mortality in hematopoietic stem cell transplantation (HSCT) patients. Individuals homozygous for the *3 mutation in cytochrome P450 3A5-encoding gene (CYP3A5) lack CYP3A5 expression, affecting tacrolimus pharmacokinetics. Here, we investigated the relationship between CYP3A5*3 polymorphism and GVHD in allogeneic HSCT patients receiving tacrolimus. The patients underwent their first allogeneic HSCT and were administered tacrolimus by continuous infusion. A quenching probe method was used to genotype the CYP3A5 6986A>G (*3 ) allele. Based on CYP3A5 polymorphism analysis results, the subjects were divided into wild-type allele-bearing (*1/*3) and non-bearing ( *3/*3) groups. The groups were compared regarding their characteristics at the time of transplantation and the frequency of acute GVHD. The *1/*3 and *3/*3 groups comprised nine and 11subjects, respectively. The frequency of acute GVHD during the observation period was higher in the *1/*3 group than in the *3/*3 group ( P = 0.049). There was a significant difference in the cumulative incidence of acute GVHD between the two groups (P = 0.019). When GVHD was observed, the blood tacrolimus concentration was close to the target concentration (10–15 ng/mL). CYP3A5*3 polymorphism could potentially predict clinical outcomes.