Impact of multidrug resistance 1 gene polymorphism on tacrolimus dose and concentration-to-dose ratio in Chinese liver transplantation recipients.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jin
Jing
J
Department of Hepatobiliary Pancretic Surgery, Key Laboratory of Combined Multi-Organ Transplantotion, First Affiliated Hospital, Zhejiang University, P. R. China.
Wu
Li-hua
LH
Wang
Wei-lin
WL
Yu
Song-feng
SF
Yan
Sheng
S
Zheng
Shu-sen
SS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016031:Liver Transplantation / Q000208:ethnology / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000008:administration & dosage*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016559:Tacrolimus