| BackgroundAccording to the latest statistics,there are currently about one million end-stage renal disease patients in China,and the incidence is increasing at an annual rate of50-100 per million people.Kidney transplantation is the most effective method for treating end-stage renal failure,but the occurrence of rejection is the main cause of kidney transplantation failure,so the rational application of immunosuppressive agents is the key to the prognosis of renal transplantation.Tacrolimus?FK506?belongs to macrolide immunosuppressant.It has a significant effect on the treatment of immune rejection after organ transplantation.Therefore,the commonly used immunosuppression regimen of tacrolimus with mycophenolate mofetil with glucocorticoid is the first-line drug for the prevention and treatment of acute rejection after kidney transplantation.Because the therapeutic window of tacrolimus is relatively narrow and there are large individual differences in oral bioavailability.CYP2D6 is a member of the cytochrome P450 supergene family.Although the CYP2D6 metabolizing enzyme accounts for only 2%of the total liver,it is involved in more than 25%of the drug metabolism activities in the clinic.The absorption and metabolism of tacrolimus is affected by the activity of the transporter?P-gp,encoded by the ABCB1 gene?,and the single nucleotide polymorphism of ABCB1 affects the pharmacokinetics of tacrolimus by encoding P-gp.OBJECTIVEIn order to effectively prevent and reduce renal transplantation and treatment of acute rejection,reduce the risk of cardiovascular disease,and improve the long-term survival rate of transplanted organs,it is very essential to monitor and analyze the wholebloodconcentrationofpatientstakingtacrolimuskidney transplantation.According to the effective blood drug concentration scope,it will be observed whether CYP2D6 and ABCB1 gene polymorphism has an effect on the blood concentration of tacrolimus after renal transplantation,and it can provide a basis for individualized medication of tacrolimus in renal transplant patients.METHODSThe data were collected from the inpatients or outpatients who performed tacrolimus blood concentration test for kidney transplantation and the need of monitoring blood concentration of tacrolimus from the First Affiliated Hospital of Zhengzhou University from February 2015 to June 2017.The blood concentration of tacrolimus was measured by chemiluminescence microparticle immunoassay?CMIA?.In this study,the blood levels of 5419 tacrolimus were collected and the results were compared with each another.Blood samples were collected from 85 patients and 90patients with renal transplant recipients,and the body weight,tacrolimus dose and plasma concentration were recorded.The genotypes of the patients were genotyped using the Sequenom MassArray system genotyping method,and then the differences of various genotypes were compared in the period of the tacrolimus blood ratio of concentration/dosage.RESULTS1.In the distribution of tacrolimus blood concentration in the renal transplantation,the concentration of less than 5.0 ng·mL-1 accounted for 13.0%of the total number of renal transplant patients,the concentration between 5.00 ng·mL-1and 20.00ng·mL-11 accounted for 85.5%,the level of higher than 20.00 ng·mL-11 accounts for1.5%.There was significant difference in the blood drug concentration between men and women of the same age group?All P<0.05?.In comparison with men of all age groups,there was no statisticalsignificance?P>0.05?.However,in the comparison of all age groups of women,the difference has statistical significance?P<0.05?.2.In the concentration/dose distribution of tacrolimus among different genotypes in kidney transplant patients,Among the CYP2D6?rs1065852?genotypes,the C/D values of patients with GG,GA and AA were 96.5?33.4,298.4??112.5?55.8,426.2??102.1?25.0,326.7?ng·mL-1·kg·mg-1,there was significant difference in C/D value of GG type and GA type?P<0.05?.In the CYP2D6?rs16947?genotype,the C/D values of patients with GG,GA and AA were 103.8?25.0,426.2??103.3?33.3,326.7??100.0?36.7,206.5?ng·mL-1·kg·mg-1,respectively,and the difference was not statistically significant?P>0.05?.3.In the ABCB1?rs2032582?genotype,the C/D values of patients with GG,GT and TT were 112.2?43.7,711.1??103.8?25.0,513.5??110.3?33.3,298.4?ng·mL-1·kg·mg-1,respectively.There was no statistically significant difference among them?P>0.05?.Among the ABCB1?rs1045642?genotypes,the C/D values of CC,CT and TT patients were 103.3?43.7,426.2??104.3?25.0,711.1??103.3?65.0,298.4?ng·mL-1·kg·mg-1,There was no significant difference?P>0.05?.The C/D values of patients with CC,CT and TT in ABCB1?rs1128503?genotype were 109.2?56.5,426.2??105.6?33.3,711.1??101.6?25.0,298.4?ng·mL-1·kg·mg-1,the difference was statistically significant?P<0.01?.CONCLUSION1.There is significant individual difference in the concentration of tacrolimus in blood.Especially there was significant difference between male and female.Among different age groups of women,the differences of tacrolimus concentration were significant.2.There was statistical significance between GG and GA at rs1065852 locus of CYP2D6 gene in the concentration/dose ratio of tacrolimus.However there was no statistical significance between GG,GA and AA genotypes of rs16947 locus of CYP2D6 gene and the ratio of concentration/dose of tacrolimus.There was statistical significance between CC and CT or TT at rs1128503 locus of ABCB1 gene in the concentration/dose ratio of tacrolimus.While the ABCB1?rs2032582?and ABCB1?rs1045642?gene polymorphisms had no statistical significance on the C/D value of tacrolimus. |
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