摘要
目的探讨MDR1C1236T、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PCR-基因测序法检测104例肾移植术后稳定期患者MDR1C1236T、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%。MDR1C3435T、MDR1TTT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,MDR1TTT单倍体与他克莫司C/D比值仍存在显著相关(P<0.05)。MDR1C1236T、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 MDR1C3435T、MDR1TTT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。
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 （P0.05） .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 .
出处
《药学实践杂志》
CAS
2015年第5期415-418,共4页
Journal of Pharmaceutical Practice
基金
漳州市科学技术局科研课题(ZZ2012J27)
