ABCB1 haplotype influences the sirolimus dose requirements in Chinese renal transplant recipients

Lee, Jun; Huang, Hongfeng; Chen, Ying; Lu, Xin-Jiang

doi:10.1002/bdd.1881

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…Therefore, the ABCB1 haplotype (including C1236T, G2677T/A and C3435T) may influence the drug pharmacokinetics more significantly [17,36]. Our previous study [39] focusing on the impact of this ABCB1 haplotype on sirolimus dose requirement demonstrated that the CGC/ CGC diplotype carrier was about 30% lower compared with those carrying the CGC/TTT or TTT/TTT diplotype. The study by Wang also reported that the C 0 /D of CsA was related to the haplotype of ABCB1 [40].…”

Section: Discussionmentioning

confidence: 99%

“…Search strategy. A computerized literature search was conducted to identify relevant articles published up to 30 July 2014in PubMed (1966-2014, Embase (1974Embase ( -2014, Medline (1966-2014) and Cochrane Library databases (Issue 7 2014). To investigate the relationship between ABCB1 C3435T polymorphism and pharmacokinetics of CsA in kidney transplant recipients, the following search terms were used: '(kidney or renal) and (transplantation or transplant or allograft or graft) and (cyclosporine or ciclosporin or cyclosporin) and (MDR1 or MDR-1 or ABCB1 or p-glycoprotein or P-gp) and (polymorphism or polymorphisms or genotype)'.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of ABCB1 C3435T Polymorphism on Cyclosporine Dose Requirements in Kidney Transplant Recipients: A Meta‐Analysis

Lee

Wang

Yang³

et al. 2015

Basic Clin Pharma Tox

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Cyclosporine A (CsA) is a substrate of the multi-drug efflux pump P-glycoprotein (P-gp) encoded by ABCB1. Among the various single nucleotide polymorphisms (SNPs) of ABCB1, C3435T has been extensively investigated to determine the relationship with the pharmacokinetics of CsA. However, the results are controversial. This meta-analysis was designed to evaluate the influence of C3435T SNP on the dose-adjusted trough (C 0 /D) and peak (C max /D) concentrations of CsA. Based on a literature search of four authoritative databases, 13 studies since 2001 concerning 1293 kidney transplant recipients were included. The results indicated a significant difference of C 0 /D and C max /D between 3435CC and 3435TT genotype carriers (weighted mean difference (WMD) of C 0 /D: 4.18 (ng ml À1 )/(mg kg À1 ), 95% CIs: 1.00-7.37, p = 0.01; WMD of C max /D: 20.85 (ng ml À1)/ (mg kg À1 ), 95% CIs: 2.25-39.46, p = 0.03). Subgroup analysis by ethnicity demonstrated that C 0 /D was lower in Asian CC versus TT genotype carriers (WMD = 10.32 (ng ml À1)/(mg kg À1 ), 95% CIs: 4.78-15.85, p = 0.0003) but did not vary by genotype for Caucasian recipients. Moreover, significant variation of C 0 /D was found at 1 week and 1-3 months after transplantation between CC and TT genotype carriers. Therefore, this meta-analysis showed a correlation between ABCB1 C3435T polymorphism and the dose-adjusted concentration of CsA. Patients with 3435CC genotype will require a higher dose of CsA to achieve target therapeutic concentrations when compared with 3435TT carriers after kidney transplantation, especially in the Asian population and especially during the early and middle time periods after transplantation.Cyclosporine A (CsA), a calcineurin inhibitor, has been widely used for kidney transplant recipients to avoid allograft rejection [1]. However, CsA has a narrow therapeutic index and large interindividual pharmacokinetic variability [2,3]. To achieve the desired efficacy and limit side-effects, the individual trough or peak CsA concentration is routinely monitored [4]. Exploring the factors behind the large interindividual variability of CsA will help to develop a more reasonable individualized dosage regimen for kidney transplantation recipients. Genetic polymorphisms of drug metabolism enzymes and drug transporters have recently been considered as an important determinant of pharmacokinetic variation [5,6].CsA is a substrate of the multi-drug efflux pump P-glycoprotein (P-gp), which acts as an ATP-dependent transmembrane transporter and limits the bioavailability of drugs by decreasing their absorption from the intestinal lumen and enhancing their excretion [7]. P-gp is encoded by the multidrug resistance gene-1 (ABCB1). More than 50 single nucleotide polymorphisms (SNPs) in the corresponding gene sequence (ABCB1) of P-gp have been identified to date. In particular, exon 12 (C1236T), exon 21 (G2677T/A) and exon 26 (C3435T) were shown to play an important role in the expression and function of P-gp and have a functional impact on the pharma...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The Effect of ABCB1 C3435T Polymorphism on Cyclosporine Dose Requirements in Kidney Transplant Recipients: A Meta‐Analysis

Lee

Wang

Yang³

et al. 2015

Basic Clin Pharma Tox

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“…Two studies on patients with renal transplantation[ 43 , 47 ] did not show any association between the ABCB1 c.3435C>T SNP and the mTORI dose. Another study[ 48 ] found that Chinese patients carrying the ABCB1CGC/CGC haplotype require a lower dose of sirolimus. ABCB1 does not seem to exert any pharmacogenetic effect on the PK of mTORIs.…”

Section: Pharmacogenetics Of Mammalian Target Of Rapamycin Inhibitorsmentioning

confidence: 99%

Pharmacogenetics of immunosuppressant drugs: A new aspect for individualized therapy

Salvadori¹,

Tsalouchos²

2020

WJT

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In recent years, pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose. Indeed, pharmacogenetics may exert its action on immunosuppressant drugs at three levels. Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation. Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants. Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways. Of course, not all genes have been discovered and studied, but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined. Other genes on the basis of relevant studies have been proposed as good candidates for future studies. Unfortunately, to date, clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney, heart and lung transplantation is recommended. The conclusions of the studies on the recommended candidate genes, together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.

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“…Six studies were excluded: 3 articles were non-relevant studies; 1 article supplied insufficient data; 1 article described as log C/D; 1 article investigated the D/C ratio. Thus, there were 6 eligible studies (10,11,(18)(19)(20)(21) described the association of ABCB1 polymorphism with the C/D ratio of SRL. These studies were conducted in different countries including China (10,18,19), Spain (20), Belgium (21), France (11).…”

Section: Studies Selection and Characteristicsmentioning

confidence: 99%

The effect of ABCB1 polymorphism on sirolimus in renal transplant recipients: a meta-analysis

Shao¹,

Hu²,

Han³

et al. 2020

Transl Androl Urol

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Background: Sirolimus (SRL) is an immunosuppressive drug and substrate of the P-glycoprotein (P-GP) encoded by ABCB1. The relationship between ABCB1 polymorphism and the pharmacokinetics of SRL in different studies were conflicting in renal transplant recipients. Thus, this meta-analysis aims to investigate the influence of ABCB1 C3435T, C1236T, and G2677T/A polymorphisms on the dose-adjusted trough level (C/D) of SRL in renal transplant recipients.Methods: PubMed, Embase, and the Cochrane Library were searched for relevant studies. The quality of each eligible study was assessed according to Newcastle-Ottawa Scale. The STATA 15.0 was adopted to perform the meta-analysis. The fixed-effects model was used for pooled results with low heterogeneity (I 2 ≤50%); otherwise, the random-effects model was used.Results: A total of 6 studies were included in the meta-analysis. Results of pooled analysis showed no significant association of SRL C/D ratio with ABCB1 C3435T polymorphism. The subgroup analysis based on different ethnic groups and different time-points after SRL initiation in renal transplant recipients were also conducted. No significant association was observed in these subgroups. Significant associations were showed between ABCB1 C1236T polymorphism and the C/D ratio of SRL in the homozygous model

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ABCB1 haplotype influences the sirolimus dose requirements in Chinese renal transplant recipients

Cited by 14 publications

References 41 publications

The Effect of ABCB1 C3435T Polymorphism on Cyclosporine Dose Requirements in Kidney Transplant Recipients: A Meta‐Analysis

The Effect of ABCB1 C3435T Polymorphism on Cyclosporine Dose Requirements in Kidney Transplant Recipients: A Meta‐Analysis

Pharmacogenetics of immunosuppressant drugs: A new aspect for individualized therapy

The effect of ABCB1 polymorphism on sirolimus in renal transplant recipients: a meta-analysis

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