Studies on the human MDR1, MRP1, and MRP2 ABC transporters: functional relevance of the genetic polymorphisms in the MDR1 and MRP1 gene

P -g lycoprotein (Pgp) is a m e m b e r of th e A B C -transporter fam ily, a n d in h u m a n s, is encoded by th e MDR1 gene.R ecently, several single-nucleotide polym orphism s in th e MDR1 gene w ere identified.T h e aim of th e presen t study w as to e v alu ate th e effect of th e MDR1 genetic poly m o rp h ism s G 2 6 7 7 T a nd C 3 4 3 5 T o n Pgp activity in C D 56+ a n d CD4+ p e rip h e ra l blood cells.U sing flow cytom etry, rh o d a m in e 123 (R h l2 3 ) efflux w a s d e te rm in e d in 4 6 m ale h e a lth y v olunteers.M edian R h l2 3 fluorescence in c o n tro l sam ple, after baseline dye u p tak e, w as set as 100% .R h l2 3 fluorescence in efflux sam ples, exposed to different efflux periods, w as used to calcu late th e p e rc en tag e o f R h l2 3 re ta in e d in th e cells in com parison w ith control.T here w as no sig n ifican t difference in R h l2 3 efflux in CD 56+ cells after 5, 10, 15, an d 3 0 m in efflux b etw een in d iv id u als w ith different MDR1 genotypes.Also, in CD4+ cells after 15, 3 0, 6 0, a n d 9 0 m in, R h l2 3 efflux did n o t reveal statistically different results for th e th re e g en o ty p es a t 2 6 7 7 a n d 3 4 3 5 .R h l2 3 efflux w as n o t e n h a n c e d by a 10-day rifam p in a d m in istra tio n , as d eterm in ed in 15 individuals before an d after rifam pin tre a tm e n t.In c o n clu sio n , w e fo u n d n o im pact of th e MDR1 G 2 6 7 7 T an d C 3435T p o ly m o rp h ism s on P g p activ ity in C D 56+ an d CD4+ perip h eral blood lym phocytes.