关键词:

细胞色素 P450 酶系 3A5 , 肾移植 , 他克莫司 , 基因多态性 ,

Abstract:

Objective To investigate the effect of polymorphisms of CYP3A5 gene mutation on the metabolism of tacrolimus in renal transplantation recipients after surgery，and to compare the differences in followup parameters of patients with different metabolic function genotypes after kidney transplantation. Methods The recipients who received allograft kidney transplantation from January 2016 to December 2018 were selectedconsecutively，and the data of each follow-up in the perioperative period of kidney transplantation and the electronicmedical record system after the operation were sorted out，mainly including the general information before the operation，the dose of tacrolimus taken at each follow-up time point（the second week，one month，three months，six months，one year and two years after the operation），the concentration-dose ratio，liver and kidney functionpostoperative complications. CYP3A5 genotype was determined by PCR-SSP method before surgery，and kidney transplant recipients were divided into CYP3A5*1 expression group（AA，AG，28 cases in total）and CYP3A5*1 non-expression group（GG，124 cases in total）according to different genotypes. The differences of clinical indicators between the two groups during the follow-up period were compared and systematically analyzed. Results In this study，a total of 152 recipients of kidney transplantation were included according to the above criteria，including 30 recipients of living donor transplants from relatives and 122 recipients of DCD transplants. There were 52 females（34.21%）with an average age of（43.90±10.81）years and an average weight of（65.51±12.02）kg. Patients were divided into groups according to the difference of CYP3A5 expression，and the preoperative basic data of CYP3A5*1 expression group（AA，AG）and non-expression group（GG）were analyzed. The results showed that there was no statistical difference in the basic demographic clinical characteristics between the two groups. The C0/D value of tacrolimus in the CYP3A5*1 expression group was significantly lower than that in the CYP3A5*1 non-expression group at week 2，month 1，3，6，year 1 and year 2 after renal transplantation（P ＜ 0.01）. Thedaily tacrolimus dose of the CYP3A5*1 expression group was also significantly lower than that of the CYP3A5*1non-expression group at each of the above follow-up time points（P ＜ 0.01）. At the 1st month and 2nd year of follow-up after kidney transplantation，the serum trough concentration of tacrolimus in CYP3A5*1 expression group was significantly lower than that in CYP3A5*1 non-expression group（P ＜ 0.01）. There was no significant difference in blood tacrolimus concentration between the two groups at the follow-up time points of 2 weeks，3 months，6 months and 1 year（P ＞ 0.05）. There were no significant differences in serum creatinine，transaminase，hemoglobin， blood glucose levels，renal biopsy pathological types and postoperative complications between the two groups at each follow-up time point（P ＞ 0.05）. Conclusion Compared with CYP3A5*1 non-expression group，patients in CYP3A5*1 expression group metabolized tacrolimus faster after taking tacrolimus，and higher tacrolimus dose is usually required to reach the target blood concentration range after transplantation. The differences of CYP3A5 gene polymorphism among different renal transplant recipients have no significant negative effects on postoperative liver and kidney function，blood glucose level，graft rejection，graft survival and adverse events. 

Key words:

CYP3A5, Kidney transplantation, Tacrolimus, Gene polymorphism