ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2017, Vol. 26 ›› Issue (6): 522-527.DOI: 10.3969/cndt.j.issn.1006-298X.2017.06.005

• 论文 • 上一篇    下一篇

CYP3A4、CYP3A5和MDR1基因多态性与肾移植受者他克莫司血药浓度的关系

  

  • 出版日期:2017-12-28 发布日期:2017-12-26

Association of CYP3A4, CYP3A5 and MDR1 polymorphisms with individual tacrolimus dosage regimen in renal transplant recipients

  • Online:2017-12-28 Published:2017-12-26

摘要:

目的:研究CYP3A4*18B、CYP3A5*3及MDR1基因突变对他克莫司血药浓度/(剂量×体重)(C/D)的影响。
方法:采用PCRRFLP方法检测227例肾移植受者CYP3A4*18B、CYP3A5*3及MDR1 C1236T、G2677T/A及C3435T基因型,比较不同基因型受者之间他克莫司的C/D值的差异。
结果:CYP3A4*18B和CYP3A5*3基因多态性与肾移植受者他克莫司C/D值具有相关性(P<001)。但是消除CYP3A5*3等位基因影响后,CYP3A4*18B各基因型间他克莫司的C/D值无显著性差异(P>005);而消除CYP3A4*18B等位基因影响后,CYP3A5*1/*1型和*1/*3型受者型受者他克莫司的C/D值显著性低于*3/*3(P<001)。MDR1各基因型组间他克莫司的C/D值均无显著性差异。
结论:消除CYP3A5*3等位基因影响后,CYP3A4*18B和MDR1基因多态性对他克莫司血药浓度无影响。

关键词: 肾移植, 他克莫司, 基因多态性, 血药浓度

Abstract:

Objective:To investigate the effect of CYP3A4*18B, CYP3A5*3 and MDR1 on concentration/dosage×body body weight ratios (C/D) of tacrolimus in renal transplant patients.
Methodology:The CYP3A4*18B, CYP3A5*3, MDR1 C1236T, G2677T/A and C3435T genotypes of 227 renal transplant patients were determined by PCRRFLP method. The differences of C/D ratios were compared among all of the genotype groups treated with tacrolimus.
Results:CYP3A4*18B and CYP3A 5*3 gene polymorphisms were associated with the C/D ratios of patients (P<001). No significant association was found between C/D of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P>005), While after the effects of CYP3A4*18B genotype was eliminated, the C/D ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group were significantly lower than those with CYP3A5*3/*3 genotype groups (P<001). There was no significant difference in the C/D ratio of tacrolimus among  MDR1 C1236T,MDR1 G2677T/A and MDR1 C3435T genotype groups.
Conclusion:CYP3A4*18B and MDR 1 gene polymorphisms do not affect blood  concentration of tacrolimus.

Key words: renal transplantation, tacrolimus, polymorphism, Blood drug concentration