Effect of CYP3A5 Gene Polymorphisms on Tacrolimus Blood Concentrations and Adverse Events in Allogeneic Hematopoietic Stem Cell Transplant Patients

• Published in: Transplantation proceedings 2024-09, Vol.56 (7), p.1678-1682
• Main Authors: Jiang, Jia, Luan, Jiajie
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Cytochrome P-450 CYP3A - genetics; Female; Genotype; Graft vs Host Disease - blood; Graft vs Host Disease - genetics; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Male; Middle Aged; Polymorphism, Genetic; Tacrolimus - blood; Transplantation, Homologous; Young Adult
• ISSN: 0041-1345; 1873-2623; 1873-2623
• DOI: 10.1016/j.transproceed.2024.08.012

Tacrolimus is the core basic immunosuppressant after transplantation. Cytochrome P450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The aim of this study was to investigate the effect of CYP3A5 gene polymorphisms on tacrolimus blood concentrations and acute graft versus host disease (GVHD) in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study included adult patients who received allo-HSCT at the First Affiliated Hospital of Wannan Medical College from January 2021 to June 2022, and received postoperative treatment with tacrolimus. Tacrolimus blood levels were obtained by fully automatic chemiluminescence immunoassay analyzer. Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 allelic variants. In a total of 50 transplant patients, 30 patients were detected with CYP3A5*3/*3 genotype, 15 patients with CYP3A5*1/*3 genotype, and 5 patients with CYP3A5*1/*1 genotype. The initial tacrolimus blood concentrations in allo-HSCT patients with CYP3A5*1/*1, *1/*3, and *3/*3 genes were 7.75, 8.61, and 10.19 ng/mL, respectively; The initial blood concentration/dose (C/D) ratios were 4.08, 4.42 and 5.66 ng/(mL·mg), respectively. The C/D ratios of allo-HSCT patients carrying CYP3A5*1/*1, *1/*3, and *3/*3 genes were 4.35 and 4.71 and 5.58, 4.19, 4.56 and 5.71 ng/(mL·mg) in the second and 3rd weeks after operation. These results showed that the blood concentration and C/D ratio of tacrolimus in patients with CYP3A5*3/*3 genotype were significantly higher than those in patients with CYP3A5*1/*3 or CYP3A5*1/*1 genotype. Moreover, the incidence of acute GVHD after allo-HSCT in patients with CYP3A5*1/*1 genotype was significantly higher than that in patients with CYP3A5*1/*3 or CYP3A5*3/*3 genotype. Most patients carry the mutant allele CYP3A5*3. CYP3A5 gene polymorphisms affect tacrolimus blood concentrations and acute GVHD after allo-HSCT.