Influence of multidrug resistant gene polymorphisms and haplotype on blood concentration of tacrolimus in individuals in stable phases after renal transplantation
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摘要: 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PCR-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,MDR1 C1236T、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。Abstract: 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 transplantation, and to provide data for personalized FK-506 administration. Methods The MDR1 C1236T, G2677T/A and C3435T genotypes 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 among 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 correlation 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 polymorphisms 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.
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Key words:
- renal transplantation /
- tacrolimus /
- MDR1 /
- polymorphisms /
- haplotype
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