OBJECTIVE: To investigate the influence of CYP3A5*3(rs776746) genetic polymorphism on blood concentration of tacrolimus (TAC) and renal function in renal transplant recipients during the stable period. METHODS: A total of 98 renal transplant recipients during the stable period receiving TAC-based triple anti-rejection scheme (TAC+sodium mycophenol+prednisone acetate) after surgery and regular follow-up were selected from our hospital during Jan. 1995-Dec. 2014. The follow-up information during Jan.-Dec. 2016 was also collected. Trough concentration of TAC in renal transplant recipients was determined by chemiluminescence microparticle immuno assay. Standard blood concentration (C/D) was calculated after corrected with body weight and daily dose. Scr level was detected with dry chemistry method. CYP3A5*3 genotype was detected by PCR-RFLP and direct sequencing. The relationship of CYP3A5*3 genetic polymorphism with TAC C/D value and Scr level was determined by Kruskal Wallis H or Mann-Whitney U assay. RESULTS: Among 98 renal transplant recipients, there were 9 cases of CYP3A5*3 *1/*1(AA) genotype, 37 cases of *1/*3(AG) genotype and 52 cases of *3/*3(GG)genotype. The gene frequencies were 9.18%, 37.76%, 53.06%, which were all in line with Hardy-Weinberg equilibrium (P>0.05). There was no statistical significance in trough concentration of TAC among different genotypes (P>0.05). There was statistical significance in TAC dose and C/D value among different genotypes (P>0.05). TAC dose of CYP3A5*3 *3/*3 genotype recipients was significantly lower than those of *1/*3 and *1/*1 genotype recipients; that of *1/*3 genotype recipients was significantly lower than that of *1/*1 genotype recipients. C/D value of *3/*3 genotype recipients was significantly higher than those of *1/*3 and *1/*1 genotype recipients; that of *1/*3 genotype recipients was significantly higher than that of *1/*1 genotype recipients, with statistical significance (P<0.05). There was no statistical significance in Scr levels among different genotypes (P>0.05). CONCLUSIONS: CYP3A5*3 genetic polymorphism significantly influences blood concentration of TAC in renal transplant recipients during the stable period, and *3 allele carriers have higher C/D values and need smaller TAC daily dose. CYP3A5*3 genetic polymorphism may be not associated with Scr level.
关键词
CYP3A5*3基因基因多态性他克莫司稳定期肾移植血药浓度肾功能
Keywords
CYP3A5*3 geneGenetic polymorphismTacrolimusStable periodRenal transplantationPlasma concentrationRenal function