| Objective: Tacrolimus is a new liposoluble macrolide immunosuppressant,which is widely used in anti-rejection therapy after liver transplantation because of its effective prevention of rejection after liver transplantation,it has become a routine drug for anti-rejection therapy after liver transplantation.But its treatment window is narrow,and the pharmacokinetics of tacrolimus is very different in different individuals,so it is necessary to closely monitor the blood concentration of tacrolimus to adjust the dosage.In this study,we found the relationship between CYP3A5 genotype and postoperative tacrolimus C/D ratio in adult liver transplant recipients by collecting peripheral blood samples and testing the CYP3A5 genotyping before transplantation.the effects of different individuals on drug absorption and metabolism of tacrolimus were discussed at the level of drug metabolism gene,which provided a reference for patients with liver transplantation to formulate a reasonable and effective individualized drug use plan for tacrolimus.Methods:98 adult liver transplant patients in the first central hospital of tianjin were selected as the study subjects,aged 35-65 years and average age 54±10years.Preoperative collection of liver transplant receptor and donor blood,using PCR to detect the CYP3A5 genotype of the donor receptor.After the operation,the same anti-rejection treatment regimen with tacrolimus as the basic immunosuppressant was used,and the body weight of the patient、dosage of tacrolimus and the concentration of grain,and the biochemical indexes of blood routine,liver and kidney function were regularly monitored.The dose of tacrolimus was daily dose per kilogram of body weight.To compare the relationship between different genotyping of donor receptor and tacrolimus C/D and to explore the significance of CYP3A5 genotype of liver transplantation donor receptor for clinical individualized drug use.Results:Of the 98 patients and their corresponding donors.In donor CYP3A5 genotyping,15 were type AA(15.3%),27 were type AG(27.6%),56 were type GG(57.1%);In receptor CYP3A5 genotyping,14 were type AA(14.3%),27 were type AG(27.6%)and 57 were type GG(58.1%);and the distribution of alleles was consistent with genetic rule,with no significant difference(P >0.05).There was no significantdifference in sex,age and body weight among the three genotypes of donor receptors(P >0.05).According to the donor genotypes were divided into AA,AG,and GG 3groups.The results showed that the plasma C/D ratio of tacrolimus GG >AG >AA,was significantly correlated with the donor CYP3A5 genotypes(p<0.05)at 1、2、3and 4 weeks after liver transplantation.The differences between groups were statistically significant(p <0.05),and the statistical differences between AA and GG groups were significant(p <0.01).According to the receptor genotypes were divided into AA,AG and GG 3 groups.The results showed that the plasma concentration/dose ratio of tacrolimus GG> AG >AA,was significantly correlated with the receptor CYP3A5 genotype at 1、2、3and 4 weeks after liver transplantation.the differences between groups were statistically significant(p <0.05),and the statistical differences between AA and GG groups were significant(p <0.01).To further explore the relationship between the donor/receptor CYP3A5 genotype and the C/D ratio of tacrolimus in patients with liver transplantation,we divided the patients into A*/A*,A*/GG,GG/A* and GG/GG 4 groups based on the receptor and donor genotype.The results showed that the blood C/D ratio A*A*< A*/GG <GG/A*< GG at 1,2,3,and 4 weeks after liver transplantation.,and the difference of tacrolimus C/D ratio between groups was statistically significant(P <0.05),while the difference of tacrolimus C/D ratio between GG/GG and A*/A* group was statistically significant(P <0.01).Conclusion: CYP3A5 is the key gene affecting the metabolism of tacrolimus,which affects the metabolism of tacrolimus by affecting the expression level of CYP3A5 enzymes in human body.To analyze the characteristics of tacrolimus drug metabolism,it can be concluded that CYP3A5 GG genotype is easier to reach the target blood drug concentration than other genotypes,so it should be careful when adjusting the dosage,and the effect of donor CYP3A5 genotype on tacrolimus drug metabolism after liver transplantation is greater than that of receptor genotype.therefore,the detection of liver transplantation donor receptor CYP3A5 genotype before transplantation can provide guidance for adjusting the dosage of tacrolimus after liver transplantation,and can also provide a reference for the establishment of individualized anti-exclusion therapy. |
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