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 language | English |
|---|---|
| Pages (from-to) | 571-573 |
| Number of pages | 3 |
| Journal | Transplantation |
| Volume | 74 |
| Issue number | 4 |
| Publication status | Published - Aug 27 2002 |
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All Science Journal Classification (ASJC) codes
- Transplantation
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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 journal › Article
}
TY - JOUR
T1 - Neurotoxicity induced by tacrolimus after liver transplantation
T2 - Relation to genetic polymorphisms of the ABCB1 (MDR1) gene
AU - Yamauchi, Atsushi
AU - Ieiri, Ichiro
AU - Kataoka, Yasufumi
AU - Tanabe, Mizuho
AU - Nishizaki, Takashi
AU - Oishi, Ryozo
AU - Higuchi, Shun
AU - Otsubo, Kenji
AU - Sugimachi, Keizo
PY - 2002/8/27
Y1 - 2002/8/27
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0037183584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037183584&partnerID=8YFLogxK
M3 - Article
C2 - 12352921
AN - SCOPUS:0037183584
VL - 74
SP - 571
EP - 573
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 4
ER -