中文摘要：

目的：研究多药耐药基因1（MDR1）基因多态性对硫嘌呤类药物转运影响的差异及产生差异的机制。方法通过构建野生型及突变型单倍型的MDR1重组质粒并进行细胞转染，考察6-巯基嘌呤在不同MDR1基因型中转运的差异，Westen blot检测不同基因型蛋白表达水平。结果与野生单倍型相比， MDR1突变单倍型外排转运6-巯基嘌呤的活性显著降低（ P＜0.05），但2种基因型的蛋白表达水平差异无统计学意义（P＞0.05），说明该转运差异不能用该转运蛋白表达水平的差异来解释。结论 MDR1不同基因型影响其对硫嘌呤类药物的外排转运，这可能是造成硫嘌呤类药物反应个体差异的原因之一；MDR1不同基因型对药物转运的影响可能不是由蛋白表达水平的差异造成的。

英文摘要：

Objective The effect of MDR1 gene polymorphism on the difference in the transportation of thiopurine and its possible mechanism were explored.Methods The recombinant plasmids of wild -type and mutant haplotype of MDR1 were constructed and transfected into cells , the difference in the transportation of 6 -thiopurine in different MDR1 haplotype were studied and the MDR 1 protein expression were analyzed.Results The 6-thiopurine-efflux activity of MDR1 mutant haplotype was significantly weaker than that of MDR 1 wild-type haplotype （ P=0.014 ） , but no difference in protein expression of the two type MDR 1 was found （ P＆gt;0.05 ） , suggesting that the difference in the 6-thiopu-rine-efflux activity between MDR 1 wild-type and mutant haplotype can-not be explained by the difference in protein expression between the two MDR1 haplotypes.Conclusion The thiopurine-efflux activity varies in different MDR1 haplotypes , which maybe is one of the reasons for the in-terindividual variations in thiopurine response.The varied effects of the different MDR1 genotype on the drug transportation are not caused by the different protein expression of MDR 1, but by the difference in MDR1 protein folding and conformation leading to the change in the drug trans-portation activity.