Impact of CYP3A5 and MDR-1 gene polymorphisms on the dose and level of tacrolimus among living-donor liver transplanted patients: single center experience

Aim of work: To assess the impact of Cytochrome P450 3A5 (CYP3A5) and multidrug resistance-1 gene (MDR-1) single nucleotide polymorphisms on the dose and blood level of tacrolimus among liver transplanted patients. Patients and methods: We enrolled a prospective study of 41 liver transplanted patien...

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Bibliographic Details
Published in:Biomarkers 2016-05, Vol.21 (4), p.335-341
Main Authors: Fathy, Mona, Kamal, Manal, Mohy, Abeer, Nabil, Ahmad
Format: Article
Language:English
Subjects:
ATP Binding Cassette Transporter, Sub-Family B - genetics
Cytochrome P-450 CYP3A - genetics
Cytochrome P450
Dose-Response Relationship, Drug
Electrophoresis, Agar Gel
Humans
Immunosuppressive Agents - therapeutic use
Liver Transplantation
Living Donors
multidrug resistance-1
Polymerase Chain Reaction
Polymorphism, Genetic
tacrolimus
Tacrolimus - therapeutic use
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Summary:Aim of work: To assess the impact of Cytochrome P450 3A5 (CYP3A5) and multidrug resistance-1 gene (MDR-1) single nucleotide polymorphisms on the dose and blood level of tacrolimus among liver transplanted patients. Patients and methods: We enrolled a prospective study of 41 liver transplanted patients. Dose-adjusted trough blood concentration (C/D ratio) was calculated. Polymerase chain reaction-restriction fragment length polymorphism followed by sequencing was done for genotyping of CYP3A5*3 (6986A > G). Results: At 1 week, 1 and 3 months C/D ratio were significantly lower in CYP3A5 expressers *1/*1 patients compared to non-expressers *3/*3. Conclusion: CYP3A5 (6986A > G) genotype, rather than MDR-1 (2677G > A/T) variant, has an impact on tacrolimus pharmacokinetics.
ISSN:1354-750X
1366-5804
DOI:10.3109/1354750X.2016.1139002