Frequencies and Association of CYP3A5 Polymorphism With Tacrolimus Concentration Among Renal Transplant Recipients in Vietnam

Transplant Proc. 2022 Oct;54(8):2140-2146. doi: 10.1016/j.transproceed.2022.07.009. Epub 2022 Sep 6.

Abstract

Background: This study aims to investigate the frequencies and association of CYP3A5 polymorphism with tacrolimus concentration among renal transplant recipients in Vietnam.

Methods: Sixty-eight kidney transplant recipients were included in this study from the department of nephrology and dialysis, Military Hospital 103. Blood samples were collected for monitoring of tacrolimus levels and determination of CYP3A5 genetic polymorphism.

Results: A total of 68 patients studied. The CYP3A5*3*3, CYP3A5*1*3, and CYP3A5*1*1 genotypes were detected in 48 (70.6%), 16 (23.5%), and 4 (5.9%), respectively. Tacrolimus concentrations were much lower in CYP3A5 expressors than in CYP3A5 nonexpressors on the first day, month 1, 3, 6, and 12 (5.98 ± 1.05 vs 6.57 ± 1.03, P = .03; 5.79 ± 1.13 vs 6.82 ± 1.05, P < .001; 4.76 ± 1.48 vs 6.73 ± 1.09, P < .001; 4.29 ± 1.64 vs 6.46 ± 1.23, P < .001; 4.20 ± 1.36 vs 6.04 ± 1.26, P < .001), respectively. Notably, the concentration/dose ratio in the CYP3A5 expressors was lower than in CYP3A5 nonexpressors at time points of follow up (P < .001). However, there were no significant differences in the age, sex, HLA mismatch, type of donors, acute rejection, and creatinine levels at time points between group of CYP3A5 expressors and those of CYP3A5 nonexpressors.

Conclusion: In conclusion, this research indicated the significant association of CYP3A5 genetic polymorphism with daily dose and tacrolimus concentrations in renal transplant recipients. This study provided a closer step to individualize the dose of tacrolimus in renal transplant patients in Vietnam.

MeSH terms

  • Cytochrome P-450 CYP3A* / genetics
  • Genotype
  • Humans
  • Immunosuppressive Agents / pharmacokinetics
  • Kidney Transplantation*
  • Polymorphism, Genetic
  • Renal Dialysis
  • Tacrolimus* / pharmacokinetics
  • Transplant Recipients
  • Vietnam

Substances

  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Immunosuppressive Agents
  • Tacrolimus