Effect of MDR1 gene polymorphism on the transportation of thiopurine and study on its possible mechanism
- VernacularTitle:多药耐药基因1基因多态性对硫嘌呤类药物转运的影响及其分子机制研究
- Author:
Yong HE
1
;
Pan CHEN
;
Xia ZHU
;
Jing FENG
;
Xue-Ding WANG
;
Min HUANG
Author Information
1. 中山大学 药学院 临床药理研究所
- Keywords:
multidrug resistance protein;
haplotype;
6-thiopurine;
molecular mechanism
- From:
The Chinese Journal of Clinical Pharmacology
2014;(4):347-349,353
- CountryChina
- Language:Chinese
-
Abstract:
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>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.
