ABCB1基因多态性对肾移植受者环孢素血浓度的影响

Effects of ABCB1 Genetic Polymorphism on Blood Concentration of Cyclosporine in Renal Transplantated Recipients

目的:研究肾移植术后患者ABCB1基因多态性对环孢素(CsA)血浓度的影响。方法:采用PCR-RFLP(聚合酶链反应-限制性片段长度多态性)方法对339名服用CsA的肾移植患者进行ABCB1基因1236C>T、2677G>T/A和3435C>T多态性检测,荧光偏振免疫法检测肾移植患者CsA血浓度。结果:在339名肾移植患者中,ABCB1基因1236C>T、2677G>T/A和3435C>T突变等位基因频率分别为64.25%、51.54%和35.75%。ABCB1 1236C>T基因多态性检测显示,在移植术后1年,CC基因型个体的CsA血谷浓度明显高于CT和TT基因型个体(P<0.05)。2677G>T/A基因多态性检测提示,在移植术后7d,杂合子GA+GT基因型携带者的C_0高于GG和AA+TT+AT基因型携带者(P<0.05)。3435C>T基因多态性检测表明:在移植术后3个月,突变纯合子TT基因型携带者的C_0低于CC和CT基因型携带者(P<0.05)。其余各时间点,上述3种基因多态性对CsA血谷浓度无明显影响(P>0.05)。结论:ABCB1基因1236C>T、2677G>T/A和3435C>T多态性对极少数时间点的CsA浓度有影响,但对绝大多数时间点的环孢素浓度无影响。

Objective： To investigate the effects of ABCB1 genetic polymorphism on the blood concentration of eyelosporine （CsA） in Chinese renal transplantated recipients. Method： ABCB1 1236C 〉 T, 2677G 〉 T/A and 3435C 〉 T genotypes were determined by PCR and restriction fragment length polymorphism （RFLP） analysis in 339 renal transplantated recipients treated by CsA. The whole blood CsA levels of the renal transplantation recipients were measured by fluorescence polarization immunoassay. Result： In the renal transplantation recipients, the frequency of ABCB1 1236C 〉 T, 2677G 〉 T/A and 3435C 〉 T mutation allele was 64.25% ,51.54% and 35.75% ,respectively. The blood trough levels of CsA in CC carriers for ABCB1 1236C 〉 T were significantly higher than those in CT and TY carriers in the first year after the transplantation （ P 〈 0.05 ）. The blood trough concentrations of CsA in GA ＋ GT carriers for ABCB1 2677G 〉 T/A were markedly increased compared with those in GG and AA ＋ TF ＋ AT carrier on the seventh clay after the J transplantation （ P 〈 0.05 ）. The blood trough levels of CsA in homozygous TF carriers for ABCB1 3435C 〉 T were lower than those in CC and CT carriers in the third month after the transplantation（P 〈 0.05 ）. No effects of ABCB1 1236C 〉 T, 2677G 〉 T/A and 3435C 〉 T genotypes on the blood trough concentration of CsA were observed at the other time-points after the transplantation （ P 〉 0.05 ）. Conclusion： The effects of ABCBI 1236C 〉 T, 2677G 〉 T/A and 3435C 〉 T polymorphism on the blood trough levels of CsA are sig- nificant at very few time-points after the transplantation,however, not notable at major time-points after the transplantation.