CAJ | 학술논문

目的：探讨MDR1 C1236T、G2677T／A和C3435T 基因多态性和单倍体对中国汉族肾移植术后稳定期患者他克莫司浓度／剂量比值的影响，为他克莫司个体化用药提供依据。方法采用PC R-基因测序法检测104例肾移植术后稳定期患者MDR1 C1236T、G2677T／A和C3435T 的基因多态性，采用均相酶免疫测定方法（EMIT法）测定他克莫司的谷浓度，比较不同基因型患者之间他克莫司血药浓度／（剂量×体质量）（C／D）比值。结果104例患者中，MDR1C1236T、G2677T／A和C3435T 突变频率分别为56．73％、55．77％和33．17％。MDR1 C3435T、MDR1 TTT单倍体与他克莫司C／D比值具有相关性（P＜0.05）。CYP3A5*3*3患者中，MDR1 TTT单倍体与他克莫司C／D比值仍存在显著相关（P＜0.05）。MDR1 C1236T、G2677T／A、CGC单倍体与他克莫司C／D比值无显著性差异（P＞0.05）。结论 MDR1 C3435T、MDR1 TTT单倍体与中国汉族肾移植术后稳定期患者他克莫司C／D比值具有显著相关性，是影响肾移植患者他克莫司浓度个体化差异的重要因素。
목적：탐토MDR1 C1236T、G2677T／A화C3435T 기인다태성화단배체대중국한족신이식술후은정기환자타극막사농도／제량비치적영향，위타극막사개체화용약제공의거。방법채용PC R-기인측서법검측104례신이식술후은정기환자MDR1 C1236T、G2677T／A화C3435T 적기인다태성，채용균상매면역측정방법（EMIT법）측정타극막사적곡농도，비교불동기인형환자지간타극막사혈약농도／（제량×체질량）（C／D）비치。결과104례환자중，MDR1C1236T、G2677T／A화C3435T 돌변빈솔분별위56．73％、55．77％화33．17％。MDR1 C3435T、MDR1 TTT단배체여타극막사C／D비치구유상관성（P＜0.05）。CYP3A5*3*3환자중，MDR1 TTT단배체여타극막사C／D비치잉존재현저상관（P＜0.05）。MDR1 C1236T、G2677T／A、CGC단배체여타극막사C／D비치무현저성차이（P＞0.05）。결론 MDR1 C3435T、MDR1 TTT단배체여중국한족신이식술후은정기환자타극막사C／D비치구유현저상관성，시영향신이식환자타극막사농도개체화차이적중요인소。
Objective To study the relevance between the polymorphisms and haplotype of multidrug resistant gene (MDR1) and the ratio of blood concentration/dosage in individuals treated by tacrolimus in stable phases post renal transplanta-tion ,and to provide data for personalized FK-506 administration .Methods The MDR1 C1236T ,G2677T/A and C3435T gen-otypes of 104 renal transplantation patients were determined by PCR followed sequencing method .The blood concentration of tacrolimus was detected by EMIT method .The differences in concentration/(dose × weight) (C/D) ratios were compared a-mong all of the genotype groups treated by tacrolimus .Results In the 104 renal transplantation recipients ,the frequency of MDR1 C1236T ,G2677T/A and C3435T mutation alleles was 56 .73% ,55 .77% and 33 .17% ,respectively .A correlation was revealed among SNP of MDR1 C3435T ,TTT haplotype and the C/D ratios (P<0.05) .In patients of CYP3A5*3*3 ,A cor-relation was also found among TTT haplotype and the C/D ratios (P< 0.05) .No difference was found among the MDR1 C1236T ,G2677T/A ,CGC haplotype and the C/D ratios (P>0.05) .Conclusion It is demonstrated that genetic polymor-phisms of MDR1 C3435T and TTT haplotype are correlated with C/D ratio of tacrolimus in Chinese renal transplant patients in stable stage .These findings affect the dose-adjusted concentration of tacrolimus individually .