CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in Chinese renal transplant recipients

Li, Danying; Teng, Rui-chen; Zhu, Huai-jun; Fang, Yun

doi:10.5414/cp201836

Cited by 27 publications

(17 citation statements)

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“…Few studies have examined the relationship between the CYP3A5 polymorphism and tacrolimus level in liver transplant patients. Moreover, the findings from these studies are inconsistent: some results showed that the receptor genotype has important implications for the metabolism of tacrolimus (Li et al, 2013;Spierings et al, 2013;Zhang et al, 2013), while other studies showed that blood tacrolimus level is more closely associated with the donor genotype (Barry and Levine, 2010;De Jonge et al, 2012;Valente et al, 2013).…”

Section: Introductionmentioning

confidence: 69%

“…Some previous studies in renal, lung, and heart transplantation have confirmed the contribution of the CYP3A5 polymorphism to individual differences in the response to tacrolimus (Hesselink et al, 2003;Zheng et al, 2003Zheng et al, , 2004Macphee et al, 2005;De Jonge et al, 2012;Li et al, 2013;Spierings et al, 2013;Zhang et al, 2013). However, in liver transplantation, the contribution of donor liver and recipient gut on tacrolimus metabolism increases the complexity of the mechanism of tacrolimus metabolism.…”

Section: Influence Of Age Time Course and Graft Liver Weight On Thementioning

confidence: 99%

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Effect of CYP3A5 gene polymorphisms on tacrolimus concentration/dosage ratio in adult liver transplant patients

Wang¹,

Liu²,

Tong³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We examined the influence of the cytochrome P450 3A5 (CYP3A5) genes in both donors and recipients on the concentrationdosage ratio (C/D) of tacrolimus in Chinese liver transplant patients. Fifty-one adult liver transplant patients who received tacrolimus were included in this study. The CYP3A5 polymorphism in donors and recipients was determined at the time of transplantation, and tacrolimusbased immunosuppressive therapy was started based on each patient's genetic constitution. The relationship between the C/D of tacrolimus for 3 months after surgery and the CYP3A5 genotype was analyzed. A stepwise regression model was used to analyze the relationship between C/D of tacrolimus and genotype, time course, age, and liver weight in liver transplant patients. Three months after liver transplantation, C/D was both affected by the CYP3A5 genotype of both the donors and (2015) the recipients. The C/D of tacrolimus in patients with the CYP3A5*1 allele or carrying CYP3A5*1 allele in the liver was lower than that in CYP3A5*3/*3 patients with the CYP3A5*3/*3 genotype in the liver (P < 0.01). The CYP3A5*1 genotype in donors as well as in patients both contributes to interindividual variation in the C/D of tacrolimus in adult liver transplantation.

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Section: Introductionmentioning

confidence: 69%

Section: Influence Of Age Time Course and Graft Liver Weight On Thementioning

confidence: 99%

Effect of CYP3A5 gene polymorphisms on tacrolimus concentration/dosage ratio in adult liver transplant patients

Wang¹,

Liu²,

Tong³

et al. 2015

Genet. Mol. Res.

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“…Numerous studies on tacrolimus pharmacokinetics in transplant recipients consistently reported that carriers of CYP3A5*3/*3 genotype require significantly lower doses for both induction and the maintenance phase of the therapy (28–38). Similar effects of CYP3A5 polymorphism on cyclosporine levels have been detected, but the reports remained largely inconsistent (29, 37, 39–41). …”

Section: The Impact Of Genetic Polymorphisms On the Metabolism And Trmentioning

confidence: 74%

“…In renal transplant patients, significantly lower daily tacrolimus dose requirements were observed in carriers of CYP3A4*18 and *22 alleles (41, 45–47), especially in CYP3A5 non-expressors (48–50). The same, but usually less, pronounced effect was detected in transplant recipients on cyclosporine therapy (40, 47, 48).…”

Section: The Impact Of Genetic Polymorphisms On the Metabolism And Trmentioning

confidence: 99%

Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature

Rančić

Dragojević-Simić

Vavic

et al. 2016

Front. Public Health

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Renal transplantation is the treatment of choice for the patients with end-stage renal failure. Genetic factors, among others, can influence variability in response to immunosuppressive drugs. Nowadays, due to restrictive health resources, the question arises whether routine pharmacogenetic analyses should be done in the renal transplant recipients or not. The aim of this literature review was to present the up-to-date information considering the economic feasibility of pharmacogenetic testing in patients subjected to renal transplantation. The organization United Network for Organ Sharing in the US estimated that total costs per renal transplant concerning these analyses were $334,300 in 2014. Pharmacogenetic testing prior to treatment initiation could be helpful to predict and assess treatment response and the risks for adverse drug reactions. This kind of testing before treatment initiation seems to be one of the most promising applications of pharmacokinetics. Although pharmacogenetic tests were found to be a cost-effective or cost-saving strategy in many cases, some authors represent another opinion. However, if the real costs of renal transplantation are recognized, the application of these tests in the standard daily practice could be considered more realistic, which additionally emphasizes the importance of future studies assessing their cost effectiveness.

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“…This results suggested that the metabolic activity of the CYP3A4*18 was relative stabilized at the early stage after LDLT when compared with the CYP3A5*3 and MDRR1-3435, and corresponded that the CYP3A4*18B genotype affects cyclosporine A pharmacokinetics during the first month following surgery in Chinese renal transplant recipients. Patients with CYP3A4*18B alleles may require higher doses of cyclosporine A to reach the target levels [23][24][25] .…”

Section: Discussionmentioning

confidence: 99%

Homogeneous phenomenon of the graft when using different genotype characteristic of recipients/donors in living donor liver transplantation

Chiu¹,

Nakano²,

Chen³

et al. 2013

WJH

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AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18 of the liver graft after living donor liver transplantation (LDLT). METHODS:We identified the proportional change of the CYP3A5*3, MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/ donor with different genotype polymorphisms and 119 liver graft biopsy samples used with the pyrosequencing technique after LDLT. Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms (SNPs). All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3, MDR1-3435 or CYP3A4*18 were excluded. RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3, MDR1-3435 and CY-P3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient. The proportional changes of G to A alleles of the 119 samples of CYP3A5*3 (included

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CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in Chinese renal transplant recipients

Cited by 27 publications

References 0 publications

Effect of CYP3A5 gene polymorphisms on tacrolimus concentration/dosage ratio in adult liver transplant patients

Effect of CYP3A5 gene polymorphisms on tacrolimus concentration/dosage ratio in adult liver transplant patients

Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature

Homogeneous phenomenon of the graft when using different genotype characteristic of recipients/donors in living donor liver transplantation

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