Impact of multidrug resistance 1 gene polymorphism on tacrolimus dose and concentration-to-dose ratio in Chinese liver transplantation recipients / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate whether the polymorphism of multidrug resistance 1 gene (MDR1) in the donors and liver transplantation recipients was correlated with interindividual variation in tacrolimus dose requirement and concentration-to-dose ratio.</p><p><b>METHODS</b>The occurrence of MDR1 3435(C-->T) polymorphism was investigated by polymerase chain reaction followed by restriction fragment length polymorphism analysis in 50 liver transplant recipients and their corresponding donors. Doses (mg/kg body weight) and dose-adjusted trough levels (ng/mL per mg/kg body weight) were compared according to allelic status for MDR1.</p><p><b>RESULTS</b>The MDR1 genotype CC was observed in 23 subjects (23%), whereas 64 (64%) were CT and 13 (13%) were TT. Tacrolimus doses required to achieve target blood concentrations were higher in the patients with MDR1 CC genotype than in the CT or TT genotype patients, and the dose-adjusted trough levels were lower. No significant differences were found in tacrolimus doses or dose-adjusted trough levels according to the donor's MDR1 genotype.</p><p><b>CONCLUSION</b>Tacrolimus dose requirement and dose-adjusted trough levels were correlated with MDR1 3435 (C-->T) polymorphism, and MDR1 3435 (C-->T) polymorphism analysis is helpful to individualize tacrolimus administration.</p>