The Relationship Between CYP3A5 Gene Polymorphism And His Concentration/Dose In Renal Transplantation Patients

Objective:To compared the differences in tacrolimus concentrations in patients with different genotypes at the same weight dose,and the difference in tacrolimus dose between genotypes at the same tacrolimus valley concentration,calculated the relationship between the concentration/dose of tacrolimus valley(CO/D)and the polymorphism of CYP3A5 gene.To summarize the individual reference of tacrolimus dose in patients with different genotypes.at the same time,the difference between the incidence of acute rejeCTion and pulmonary infection in patients with three genotypes was compared.Methods:Selection the number of 150patients who performed the kidney transplantation form donation after the death of a citizen and whose immunosuppression scheme was tacrolimus + mycophenolate + prednisone.Extracted the DNA from these patients,analyzed their genotypes polymorphism of CYP3A5.To compare the difference about tacrolimus concentration in the same quality of tacrolimus unit dose(mg/kg)among genotype*1/*1(wild homozygous),*1/*3(heterozygous mutations),and*3/*3(homozygous mutant).Compare the the unit mass dose until the target concentration(tacrolimus 7-10ng/ml)was reached among the three groups.Compare the incidence of acute rejection and pulmonary infection in three groups of patients.Result:Among 150 patients,the CYP3A5*1/*1 type was 11 cases(7.33%),*1/*3 type was 38(25.33%),and*3/*3 was 101 cases(67.33%).Respectively the concentration of tacrolimus in the three groups of patients was 4.84±2.76、6.41 ±3.52and6.87±3.82.The quality dose of tacrolimus in the three groups was respectively 0.110±0.014/0.081 ±0.032 and 0.076±0.037 when at the time of reaching the target tacrolimus concentration.The incidence of acute rejection in the three groups was 4.3%,4.9%and 5.5%respectively.The incidence of pulmonary infection in the three groups was 2.2%,5.8%and 6.1%respectively.The tacrolimus concentration/dose ratio of*1/*1 was significantly lower than*1/*3 and*3/*3(the difference was statistically significant,P<0.01);but there was no statistically significant difference between the concentration/dose ratio of 1/*3 and*3/*3(P>0.05);There was no significant difference in the incidence of acute rejection in the three groups(P>0.05);The incidence of pulmonary infection in*1/*1 was significantly lower than that in*1/*3 and*3/*3 patients(P<0.05).Conclusion:The different genotypes of CYP3A5 lead to differences in the metabolic level of the patients and than result the difference in concentration,the concentration of tacrolimus in patients with the same unit mass dosage*1/*3 and*3/*3 was significantly higher than that in*1/*1 patients.It may be that the incidence of pulmonary infection in*1/*3 and*3/*3 patients is higher than that of*1/*1 patients.Therefore,according to the patient CYP3A5 genotype,we can use the tacrolimus individualized.Not only can the concentration be controlled at the target level more efficiently in the early stages of using tacrolimus,but also we can be avoided complications such as pulmonary infection because of the high concentration of tacrolimus and the strong immune suppression to a large extent.