Clinical Research Papers:
Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients
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Lihui Qu1,2,3,4,*, Yingying Lu1,2,3,4,*, Meike Ying1,2,3,4, Bingjue Li1,2,3,4, Chunhua Weng1,2,3,4, Zhoutao Xie 1,2,3,4, Ludan Liang1,2,3,4, Chuan Lin1,2,3,4, Xian Yang1,2,3,4, Shi Feng1,2,3,4, Yucheng Wang1,2,3,4, Xiujin Shen1,2,3,4, Qin Zhou1,2,3,4, Ying Chen1,2,3,4, Zhimin Chen1,2,3,4, Jianyong Wu1,2,3,4, Weiqiang Lin1,2,3,4,9, Yi Shen8, Jing Qin5,7, Hang Xu5, Feng Xu5,7, Junwen Wang6,8, Jianghua Chen1,2,3,4, Hong Jiang1,2,3,4, Hongfeng Huang1,2,3,4
1 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
2 Kidney Disease Immunology Laboratory, The Third Grade Laboratory, State Administration Of Traditional Chinese Medicine Of PR China, Hangzhou, China
3 Key Laboratory Of Multiple Organ Transplantation, Ministry Of Health, Hangzhou, China
4 Key Laboratory Of Nephropathy, Zhejiang Province, Hangzhou, China
5 Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
6 Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
7 Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, Guangdong, China
8 Department of Epidemiology, College of Medicine, Zhejiang University, Hangzhou, China
9 Institute of Translational Medicine, College of Medicine, Zhejiang University, Hangzhou, China
* These authors contributed to this work equally
Hongfeng Huang, email:
Hong Jiang, email:
Jianghua Chen, email:
Junwen Wang, email:
Keywords: CYP3A5, FK506, renal transplantation, acute rejection
Received: September 23, 2016 Accepted: March 08, 2017 Published: May 24, 2017
Tacrolimus (FK506) and cyclosporine A (CsA) are widely used to protect graft function after renal transplantation. The aim of the present study is to determine whether the single nucleotide polymorphism of CYP3A5 is a predictive index of FK506 dose requirement, and also the selection yardstick of FK506 or CsA treatment.We tested archival peripheral blood of 218 kidney recipients for CYP3A5 genotyping with PCR-SSP. Meanwhile, the dose of FK506 and CsA was recorded, blood concentration of the drugs was measured, and graft outcome was monitored.These results indicate that CYP3A5*AA/AG carriers need higher FK506 dose than CYP3A5*GG homozygote to achieve the target blood concentration. For CYP3A5*GG carriers, taking FK506 or CsA are both advisable. CYP3A5*AA/AG carriers preferred to CsA treatment depending on the graft outcomes and drug costs. CYP3A5 genotyping is a new approach to detecting FK506 dose requirement and a predictive index for the FK506 or CsA treatment selection in kidney recipients.
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