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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)
作者单位
邱晓燕1 武卓1 徐璐扬1 张明2 钟明康1 复旦大学附属华山医院 1. 临床药学室2. 肾病科 上海 200040 
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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(C0)。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 (C0) 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 C0 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 C0 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.
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