. 2017 May 24;8(46):81285-81294.

doi: 10.18632/oncotarget.18150. eCollection 2017 Oct 6.

Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients

Lihui Qu^#^{1

2

3

4}, Yingying Lu^#^{1

2

3

4}, Meike Ying^{1

2

3

4}, Bingjue Li^{1

2

3

4}, Chunhua Weng^{1

2

3

4}, Zhoutao Xie^{1

2

3

4}, Ludan Liang^{1

2

3

4}, Chuan Lin^{1

2

3

4}, Xian Yang^{1

2

3

4}, Shi Feng^{1

2

3

4}, Yucheng Wang^{1

2

3

4}, Xiujin Shen^{1

2

3

4}, Qin Zhou^{1

2

3

4}, Ying Chen^{1

2

3

4}, Zhimin Chen^{1

2

3

4}, Jianyong Wu^{1

2

3

4}, Weiqiang Lin^{1

2

3

4

4

5}, Yi Shen⁶, Jing Qin^{7

8}, Hang Xu⁷, Feng Xu^{7

8}, Junwen Wang^{9

6}, Jianghua Chen^{1

2

3

4}, Hong Jiang^{1

2

3

4}, Hongfeng Huang^{1

2

3

4}

Affiliations

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 Institute of Translational Medicine, College of Medicine, Zhejiang University, Hangzhou, China.
⁶ Department of Epidemiology, College of Medicine, Zhejiang University, Hangzhou, China.
⁷ Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁸ Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, Guangdong, China.
⁹ Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

^# Contributed equally.

PMID: 29113387
PMCID: PMC5655282
DOI: 10.18632/oncotarget.18150

Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients

Lihui Qu et al. Oncotarget. 2017.

. 2017 May 24;8(46):81285-81294.

doi: 10.18632/oncotarget.18150. eCollection 2017 Oct 6.

Authors

Affiliations

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 Institute of Translational Medicine, College of Medicine, Zhejiang University, Hangzhou, China.
⁶ Department of Epidemiology, College of Medicine, Zhejiang University, Hangzhou, China.
⁷ Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁸ Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, Guangdong, China.
⁹ Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

^# Contributed equally.

PMID: 29113387
PMCID: PMC5655282
DOI: 10.18632/oncotarget.18150

Erratum in

Correction: Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients.
Qu L, Lu Y, Ying M, Li B, Weng C, Xie Z, Liang L, Lin C, Yang X, Feng S, Wang Y, Shen X, Zhou Q, Chen Y, Chen Z, Wu J, Lin W, Shen Y, Qin J, Xu H, Xu F, Wang J, Chen J, Jiang H, Huang H. Qu L, et al. Oncotarget. 2020 Apr 21;11(16):1474-1477. doi: 10.18632/oncotarget.27561. eCollection 2020 Apr 21. Oncotarget. 2020. PMID: 32363004 Free PMC article.

Abstract

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.

Keywords: CYP3A5; FK506; acute rejection; renal transplantation.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no competing financial interests.

Figures

**Figure 1. FK506 dose adjusted concentration related to CYP3A5 genotype**
FK506 blood concentrations **A.,** FK506 standardized dose **B.,** and dose normalized FK506 concentration **C.,** of CYP3A5* GG recipients and CYP3A5* AA/AG recipients at 7th day, 1^st month, 3^rd month, 6^th month and 12^th month after the kidney transplantation. NS: not significant, **: p < 0.01, ****: p < 0.0001. Error bars in graphs indicates SEM.

**Figure 2. CsA dose adjusted concentration related to CYP3A5 genotype**
CsA blood concentrations A., CsA standardized dose B. and dose normalized CsA concentration C. of CYP3A5* GG recipients and CYP3A5* AA/AG recipients at 7th day, 1^st month, 3^rd month, 6^th month and 12^th month after the kidney transplantation. NS: not significant. Error bars in graphs indicates SEM.

**Figure 3. Clinical parameters of liver and kidney injury related to CYP3A5 genotype and different immunosuppressors**
Clinical parameters of kidney function, Scr A., BUN B. and liver injury, ALT C., AST **D.,** for each recipient was measured in 7 day, 1^st month, 3^rd month, 6^th month and 12^th month after the kidney transplantation. NS: not significant. Error bars in graphs indicates SEM.

**Figure 4. Costs of patients related to CYP3A5 genotype and different immunosuppressors**
Participants’ cost of immunosuppressive agents of different CYP3A5 genotypes. NS: not significant, *: p < 0.05, **: p < 0.01, ****: p < 0.0001, Error bars in graphs indicates SEM.

See this image and copyright information in PMC

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Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients

Affiliations

Tacrolimus dose requirement based on the CYP3A5 genotype in renal transplant patients

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

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References

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