肝移植中他克莫司的血药浓度与多药耐药基因多态性的关系

目的探讨肝移植术后患者的多药耐药基因（MDR1）C3435T、G2677T／A和C1236T位点的基因多态性对他克莫司（F1〈506）血药浓度的影响。方法使用荧光偏振免疫分析法（AxSYM）测定42例肝移植患者在术后1周和1个月时FK506的血药浓度，使用等位基因特异扩增法（ASA-PCR）对患者进行MDR1基因分型，比较不同基因型之间FK506的浓度／剂量比的差异。结果在42例患者中，C3435T中CC型16例（38．1％），CT型23例（54．8％），TT型3例（7．1％）；G2677T／A中CA；型4例（9．5％），GT型13例（31．O％），TT型8例（19．0％），GA型7例（16．7％），AT型10例（23．8％）；C1236T中CC型6例（14．3％），CT型19例（45．2％），TT型17例（40．5％）。根据移植术后第1周和第1个月的记录，在C1236T中CC型患者的浓度／剂量比小于CT型和TT型，且差异有统计学意义（P〈0．05）。在C3435T和G2677T／A中不同基因型之间的浓度／剂量比的差异无统计学意义（P〉0．05）。结论在肝移植患者中MDR1多态性与FK506血药浓度具有相关性，C1236TCC型患者拟取得相似的血药浓度要比CT型和TT型患者服用更高剂量的FK506。

Relationship between multi-drug resistance gene genetic polymorphism and blood concentration of tacrolimus in liver transplant patients

AIM To investigate the relationship between multi-drug resistance gene（MDR1） C3435T, G2677T/A and C1236T polymorphism and whole blood concentration of FK506 in liver transplant patients. METHODS One week and one month after the transplantation AxSYM was used to measure the whole blood concentration of FK506. The FK506 concentrations standardized by dosage and body weight （FK506 concentration per dose/kg） were compared among the several subgroups within the MDR1 C3435T, G2677T/A and C1236T. RESULTS Of the 42 patients 6（ 14.3% ）, 19 （45.2%）, 17（40.5%） were carriers of CO, CT and TI＇in C1236T, 4（9.5%）, 13（31.0%）, 8（19.0%）, 7 （16.7%）, 10（23.8%）were carriers of GG, GT, TF, GA and AT in G2677T/A, 16（38.1%）, 23（54.8%）, 3 （7.1%） were carriers of CC, CT and rlT in C3435T respertively. For C1236T, the dose ratio with CC was remarkably lower than that of those with CT and TT（ P 〈 0.05）. For C3435T and G2677T/A, there was not a significant difference among the several subgroups （ P 〉 0.05）. CONCLUSION The MDR1 genetic polymorphism is correlated with the whole blood concentration of FK506. To obtain the similar blood concentration of FK506, the patients with CC should take the drug at a higher dose than those with CT and TT.