Neurotoxicity induced by tacrolimus after liver transplantation: Relation to genetic polymorphisms of the ABCB1 (MDR1) gene

Atsushi Yamauchi, Ichiro Ieiri, Yasufumi Kataoka, Mizuho Tanabe, Takashi Nishizaki, Ryozo Oishi, Shun Higuchi, Kenji Otsubo, Keizo Sugimachi

Research output: Contribution to journalArticle

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Abstract

Background. Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. Methods. The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. Results. High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. Conclusion. It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.

Original languageEnglish
Pages (from-to)571-573
Number of pages3
JournalTransplantation
Volume74
Issue number4
Publication statusPublished - Aug 27 2002

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Tacrolimus
Genetic Polymorphisms
Liver Transplantation
Genes
P-Glycoprotein
Mutation
Discriminant Analysis
Liver Diseases
Exons
Genotype
Transplants
Weights and Measures
Polymerase Chain Reaction
Liver
Brain

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Yamauchi, A., Ieiri, I., Kataoka, Y., Tanabe, M., Nishizaki, T., Oishi, R., ... Sugimachi, K. (2002). Neurotoxicity induced by tacrolimus after liver transplantation: Relation to genetic polymorphisms of the ABCB1 (MDR1) gene. Transplantation, 74(4), 571-573.

Neurotoxicity induced by tacrolimus after liver transplantation : Relation to genetic polymorphisms of the ABCB1 (MDR1) gene. / Yamauchi, Atsushi; Ieiri, Ichiro; Kataoka, Yasufumi; Tanabe, Mizuho; Nishizaki, Takashi; Oishi, Ryozo; Higuchi, Shun; Otsubo, Kenji; Sugimachi, Keizo.

In: Transplantation, Vol. 74, No. 4, 27.08.2002, p. 571-573.

Research output: Contribution to journalArticle

Yamauchi, A, Ieiri, I, Kataoka, Y, Tanabe, M, Nishizaki, T, Oishi, R, Higuchi, S, Otsubo, K & Sugimachi, K 2002, 'Neurotoxicity induced by tacrolimus after liver transplantation: Relation to genetic polymorphisms of the ABCB1 (MDR1) gene', Transplantation, vol. 74, no. 4, pp. 571-573.
Yamauchi, Atsushi ; Ieiri, Ichiro ; Kataoka, Yasufumi ; Tanabe, Mizuho ; Nishizaki, Takashi ; Oishi, Ryozo ; Higuchi, Shun ; Otsubo, Kenji ; Sugimachi, Keizo. / Neurotoxicity induced by tacrolimus after liver transplantation : Relation to genetic polymorphisms of the ABCB1 (MDR1) gene. In: Transplantation. 2002 ; Vol. 74, No. 4. pp. 571-573.
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AU - Nishizaki, Takashi

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AB - Background. Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. Methods. The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. Results. High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. Conclusion. It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.

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