Influence of CYP3A5*3 Genetic Polymorphism on Blood Concentration of Tacrolimus and Renal Function in Renal Transplant Recipients during the Stable Period / 中国药房

ABSTRACT

OBJECTIVE:To investigate the influence of CYP3A5*3 (rs776746) genetic polymorphism on blood concentration of tacmlimus (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 +predrnisone 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.CYP3AS*3 genetic polymorphism may be not associated with Scr level.