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孙家钰, 王宪刚, 邹远高, 等. 肝肾移植患者CYP3A5和MDR1基因多态性与他克莫司浓度/剂量比的关系[J]. koko体育app 学报(医学版), 2013, 44(4): 573-577.
引用本文: 孙家钰, 王宪刚, 邹远高, 等. 肝肾移植患者CYP3A5和MDR1基因多态性与他克莫司浓度/剂量比的关系[J]. koko体育app 学报(医学版), 2013, 44(4): 573-577.
SUN Jia-yu, WANG Xian-gang, ZOU Yuan-gao, et al. Association of CYP3A5 and MDR1 Genetic Polymorphisms with the Blood Concentration of Tacrolimus in Chinese Liver and Renal Transplant Recipients[J]. Journal of Sichuan University (Medical Sciences), 2013, 44(4): 573-577.
Citation: SUN Jia-yu, WANG Xian-gang, ZOU Yuan-gao, et al. Association of CYP3A5 and MDR💃1 Genetic Polymorphisms with the Blood Concentration of Tacrolimus in Chinese Liver and Renal Transplant Recipients[J]. Journal of Sichuan University (Medical Sciences), 2013, 44(4): 573-577.

肝肾移植患者CYP3A5和MDR1基因多态性与他克莫司浓度/剂量比的关系

Association of CYP3A5 and MDR1 Genetic Polymorphisms with the Blood Concentration of Tacrolimus in Chinese Liver and Renal Transplant Recipients

  • 摘要: 目的 研究肝肾移植患者细胞色素P450(cytochrome P450,CYP)3A5和多耐药(multidrug resistance 1,MDR1)基因多态性与他克莫司浓度/剂量比(C/D值)的关系,探讨指导临床个体化用药的可行性。 方法 采用酶扩大免疫法测定60例肝肾移植患者他克莫司稳态谷浓度,以单位体质量服药日剂量校正血药浓度为浓度/剂量比(C/D值);采用实时荧光定量聚合酶链式反应(RT-PCR)法检测患者CYP3A5 A6986G和MDR1 C3435T、G2677T/A及T1236C的单核苷酸多态性(SNPs),比较不同基因型患者之间他克莫司C/D值。 结果 携带CYP3A5*1/*1型者5例,*1/*3 22例,*3/*3 33例,凡携带有*1等位基因者的C/D值(130.40±53.94)明显低于*3/*3型患者的C/D值(198.12±90.80,P<0.01)。MDR1基因C3435T位点C/C型22例,C/T型23例,T/T型15例;T1236C位点T/T型8例,T/C型32例,C/C型20例;G2677T/A位点G/G型9例,G/T型24例,G/A型5例,T/A型8例,T/T型14例,A/A型0例。MDR1的T1236C、G2677T/A和C3435T各基因型的他克莫司C/D值未发现明显差异。 结论 CYP3A5 A6986G基因多态性可以作为他克莫司个体化用药的依据,CYP3A5*3*3携带者较携带有一条CYP3A5*1等位基因的患者可减少他克莫司的给药剂量。MDR1的T1236C、G2677T/A和C3435T基因多态性与他克莫司血药浓度之间的关系尚需扩大样本量进一步研究。  
    Abstract: Objective To investigate the association of CYP3A5 and MDR1 genetic polymorphisms with the concentration/dose (C/D) ratio of tacrolimus for the feasibility of individualized medication. Methods The concentration of tacrolimus was detected by enzyme-multiplied immunoassay technique, and was adjusted by weight and dosage to C/D ratios. The single nucleotide polymorphisms of CYP3A5 A6986G and MDR1 C3435T, G2677T/A, T1236C were determined by TaqMan® RT-PCR.The differences of C/D ratio were compared among all of the genotype groups. Results There were 5 cases with CYP3A5*1/*1, 22 cases with CYP3A5*1/*3, and 33 cases with CYP3A5*3/*3. The C/D ratios of the patients with at least one CYP3A5*1 allele (130.40±53.94) was significantly lower than those with CYP3A5*3/*3 (198.12±90.80) (P<0.01). For MDR1, there were 22, 23 and 15 recipients carried C/C, C/T and T/T respectively in C3435T, and 8, 32 and 20 recipients carried T/T, T/C and C/C respectively in T1236C. The carriers with G/G, G/T, G/A, T/A, T/T were 9, 24, 5, 8 and 14 respectively in G2677T/A. No significant difference was found in the C/D ratios of tacrolimus among different MDR1 genotypes. Conclusions Determination of CYP3A5 genotype could help individualize tacrolimus dose regimen prospectively. The patients with CYP3A5*3*3 require less dose of tacrolimus to reach the same concentrations comparing with the patients with at least one CYP3A5*1 allele.  
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