Journal ArticleDOI
Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation.
Masakatsu Yanagimachi,Takuya Naruto,Reo Tanoshima,Hiromi Kato,Tomoko Yokosuka,Ryosuke Kajiwara,Hisaki Fujii,Fumiko Tanaka,Hiroaki Goto,Tatsuhiko Yagihashi,Kenjiro Kosaki,Shumpei Yokota +11 more
TLDR
Yanagimachi et al. as mentioned in this paper found that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI-related neurotoxicity after hematopoietic stem cell transplant.Abstract:
Yanagimachi M, Naruto T, Tanoshima R, Kato H, Yokosuka T, Kajiwara R, Fujii H, Tanaka F, Goto H, Yagihashi T, Kosaki K, Yokota S. Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation. Clin Transplant 2010: 24: 855–861. © 2009 John Wiley & Sons A/S.
Abstract: Background: One severe side effect of calcineurin inhibitors (CNIs: such as cyclosporine [CsA] and tacrolimus [FK506]) is neurotoxicity. CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp), encoded by ABCB1 gene. In the present study, we hypothesized that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI-related neurotoxicity.
Methods: The effects of the polymorphisms, such as CYP3A5 A6986G, ABCB1 C1236T, G2677T/A, and C3435T, associated with CNI-related neurotoxicity were evaluated in 63 patients with hematopoietic stem cell transplantation.
Results: Of the 63 cases, 15 cases developed CNI-related neurotoxicity. In the CsA patient group (n = 30), age (p = 0.008), hypertension (p = 0.017), renal dysfunction (p < 0.001), ABCB1 C1236T (p < 0.001), and G2677T/A (p = 0.014) were associated with neurotoxicities. The CC genotype at ABCB1 C1236T was associated with it, but not significantly so (p = 0.07), adjusted for age, hypertension, and renal dysfunction. In the FK506 patient group (n = 33), CYP3A5 A6986G (p < 0.001), and ABCB1 C1236T (p = 0.002) were associated with neurotoxicity. At least one A allele at CYP3A5 A6986G (expressor genotype) was strongly associated with it according to logistic regression analysis (p = 0.01; OR, 8.5; 95% CI, 1.4–51.4).
Conclusion: The polymorphisms in CYP3A5 and ABCB1 genes were associated with CNI-related neurotoxicity. This outcome is probably because of CYP3A5 or P-gp functions or metabolites of CNIs.read more
Citations
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Journal ArticleDOI
The Role of Pharmacogenetics in the Disposition of and Response to Tacrolimus in Solid Organ Transplantation
TL;DR: A randomised controlled study in kidney transplant recipients has demonstrated that a CYP3A5 genotype-based approach to tacrolimus dosing leads to more patients reaching the target concentration early after transplantation, but no improvement of clinical outcomes was observed, which may have been the result of the design of this particular study.
Book ChapterDOI
P-glycoprotein: tissue distribution, substrates, and functional consequences of genetic variations
TL;DR: Current knowledge of the functional significance genetic variants of ABC membrane transporters does not allow selection of a particular SNP to predict an individual's pharmacokinetics.
Journal ArticleDOI
PharmGKB summary: cyclosporine and tacrolimus pathways.
TL;DR: Tacrolimus (FK506) and cyclosporine (cyclosporin A, CsA) are cornerstone immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection.
Journal ArticleDOI
Pharmacokinetics and Toxicity of Tacrolimus Early After Heart and Lung Transplantation.
Maaike A. Sikma,E.M. van Maarseveen,E.A. van de Graaf,J. H. Kirkels,Marianne C. Verhaar,Dirk W. Donker,Jozef Kesecioglu,Jan Meulenbelt +7 more
TL;DR: This review focuses on posttransplant tacrolimus pharmacokinetics, and discusses relevant factors influencing the unbound tacolimus concentrations and tacro Limus (nephro‐) toxicity in heart and lung transplantation patients.
Journal ArticleDOI
Polymorphisms of the drug transporters ABCB1, ABCG2, ABCC2 and ABCC3 and their impact on drug bioavailability and clinical relevance
Oliver Bruhn,Ingolf Cascorbi +1 more
TL;DR: Variation of bioavailability and drug response may be attributed only by a small amount to polymorphisms in transporter genes, whereas transcriptional regulation or post-transcriptional modification seems to be more critical.
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