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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。
Objective To study the effects of multidrug resistance gene 1 (MDR1) gene polymorphism on the transport of thiopurines and its mechanism. Methods The wild-type and mutant haplotype MDR1 recombinant plasmids were constructed and transfected into cells to investigate the difference of 6-mercaptopurine transport in different MDR1 genotypes. Westen blot was used to detect the expression of different genotypes. Results Compared with the wild haplotypes, the activity of haplotype MDR1 translocation 6-mercaptopurine was significantly decreased (P <0.05), but there was no significant difference between the two genotypes (P> 0.05) , Indicating that this difference in translocation can not be explained by the difference in the expression level of the transporter. Conclusion Different genotypes of MDR1 affect the efflux transport of thiopurines, which may be one of the reasons for the differences in the responses of thiopurines to drugs. The effects of different MDR1 genotypes on drug transport may not be related to the differences in protein expression levels Caused.