|
| CYP3A4、CYP3A5和CYP3A7的基因多态性对中国汉族肾移植患者他克莫司药动学的影响 |
| Influence of CYP3A4, CYP3A5 and CYP3A7 Polymorphisms on Tacrolimus Pharmacokinetics in Chinese Renal Transplant Patients |
| |
| DOI： |
| 中文关键词: 他克莫司 CYP3A5 CYP3A7 P 糖蛋白 单核苷酸多态性 肾移植 |
| 英文关键词:Tacrolimus CYP3A5 CYP3A7 P glycoprotein Polymorphisms Renal transplantation |
| 基金项目:国家自然科学基金青年科学基金项目（编号：81302854），上海市自然科学基金面上项目（编号：13ZR1405200），上海市“医苑新星”青年医学人才培养资助计划项目（编号：沪卫计药政[2018]1号） |
|
| 摘要点击次数: 1077 |
| 全文下载次数: 891 |
| 中文摘要: |
| 摘 要 目的：探讨中国汉族肾移植患者中，CYP3A5*3（rs776746）、CYP3A4*1G(rs2242480)、CYP3A4 rs4646437、CYP3A7 rs2257401及CYP3A7 rs10211单核苷酸多态性对免疫抑制药他克莫司（TAC）药动学的影响。方法：采用直接测序法，对85例肾移植的患者进行基因分型。采用酶放大免疫分析法测定患者TAC的谷浓度（C0）。比较不同基因型患者间TAC浓度剂量比值的差异。结果：在85例肾移植患者中，CYP3A5*3 A、CYP3A4*1G T、CYP3A4 rs4646437 T、CYP3A7 rs2257401C及CYP3A7 rs10211 G等位基因的频率分别为29.4%,27.6%,13.5%,26.5%及27.6%。肾移植术后1个月时，CYP3A5*3、CYP3A7 rs2257401及CYP3A7 rs10211影响TAC的谷浓度（P<0.01）。CYP3A5*3 A、CYP3A7 rs2257401 C及CYP3A7 rs10211 G等位基因携带者，TAC剂量校正浓度分别比其相应非携带者剂量校正浓度低约50%左右。而本研究未发现CYP3A4*1G和CYP3A4 rs4646437基因多态性与TAC校正谷浓度相关（P>0.05）。结论：在中国汉族肾移植患者中，CYP3A5*3、CYP3A7 rs2257401及CYP3A7 rs10211的单核苷酸多态性与移植术后1个月内TAC的药代动力学有相关性，但把这种相关性应用在临床上，以优化他克莫司的剂量，尚待进一步的研究。 |
| 英文摘要: |
| ABSTRACT Objective:The purpose of this study was to investigate the potential impact of single nucleotide polymorphisms like CYP3A5*3（rs776746），CYP3A4*1G(rs2242480), CYP3A4 rs4646437, CYP3A7 rs2257401 and CYP3A7 rs10211 on the pharmacokinetics of tacrolimus in Chinese renal transplant patients. Methods: Using direct sequencing, genotypes was detected in 85 renal transplant patients. The concentrations (C0) of tacrolimus was measured with enzyme amplification immunoassay. The TAC concentration dosage ratio of different genotypes were compared. Results: In 85 renal transplantation patients, the frequency of CYP3A5*3 A, CYP3A4*1G T, CYP3A4 rs4646437 T, CYP3A7 rs2257401C and CYP3A7 rs10211G allele were 29.4%, 27.6%, 13.5%, 26.5% and 27.6%. One month after kidney transplantation, the TAC C0 were influenced by CYP3A5*3, CYP3A7 rs2257401 and CYP3A7 rs10211 (P<0.01). In patients with CYP3A5*3 A, CYP3A7 rs2257401 and CYP3A7 rs10211 G allele, the TAC C0 were about 50% lower than those non carriers. In addition, there were no significant differences in tacrolimus concentration between CYP3A7 rs10211 G and CYP3A4 rs4646437 allele (P>0.05). Conclusion: In Chinese renal transplant patients, it had the correlation between single nucleotide polymorphisms of CYP3A5*3, CYP3A7 rs2257401 and CYP3A7 rs10211 and pharmacokinetics of TAC within 1 month post transplant surgery. But it needed further research to put it into use clinically as to optimize tacrolimus dosage. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
