Impact of FOXP3 Polymorphisms on the Blood Level of Tacrolimus in Renal Transplant Recipients.

Abstract

Tacrolimus is an immunosuppressive medication for organ transplantation. FOXP3(+) T regulatory cells (Tregs) play roles in suppression of rejection and induction of graft tolerance. This study aimed to evaluate the correlation between the polymorphism of FOXP3 and the blood level of tacrolimus in renal transplant recipients. This retrospective study included 100 renal transplant recipients receiving tacrolimus treatment and 100 healthy control subjects. Genotyping for FOXP3 rs3761547 AA, AG, GG, rs3761548 AA, AC, CC and rs223236 AA, AG, GG was performed. Concentrations of tacrolimus, creatinine, and urea nitrogen levels in blood were measured. Frequencies of genotypes of FOXP3 rs3761548 AA, AC, and CC, rs3761547 AA, AG, GG and rs 223236 AA, AG, GG in renal transplant recipients were similar to those in normal people. The blood level of tacrolimus in recipients with rs3761548 CC was significantly higher than that in recipients with rs3761548 AA and AC (P< .001). No difference in the blood level of tacrolimus was found in recipients with different genotypes of rs3761547 and rs223236. Compared to rs3761548 AA and AC groups, there was no difference of Modification of Diet in Renal Disease (MDRD) glomerular filtration rate and the level of blood urea nitrogen before transplantation; however, these 2 parameters were significantly improved after transplantation in the rs3761548 CC group. The level of tacrolimus was correlated positively with MDRD glomerular filtration rate and negatively with the blood urea nitrogen level in recipients with rs3761548 CC genotype after transplantation. Our study identified a new relationship between FOXP3 rs3761548 and the blood level of tacrolimus. These results suggest that the polymorphism of FOXP3 may affect tacrolimus pharmacokinetics.