MDR1基因多态性对肝移植受体普乐可复治疗的影响

目的探讨普乐可复（Tacrolimus，FK506）服用剂量和血药浓度的个体差异与供受体多药耐药基因1（multidrug resistance gene 1，MDR1）多态性的关系。方法监测50例口服普乐可复的肝移植受体体重、服药剂量、全血谷浓度，用PCR-限制性片段长度多态性分析的方法检测供受体MDR1第3435位C／T基因型，计算每日每公斤体重的FK506用量和血药浓度与每日每公斤体重的FX505用量的比值，并分析与供受体MDR1基因型的关系。结果在各50例供受体研究中，23％为MDR1 CC基因型，54％为CT基因型，13％为TT基因型。MDR1 CC基因型受体的每日每公斤体重的FK506用量明显高于CT和TT基因型受体，前者血药浓度与每日每公斤体重的FK506用量的比值显著低于后两者，供体MDR1基因型对此无明显影响。结论普乐可复服用剂量和血药浓度与受体的MDR1第3435位点基因多态性相关。MDRI多态性分析可指导肝移植受体普乐可复临床用药的个体化。

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. CONCLUSION: 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.