Journal
PHARMACOGENETICS
Volume 11, Issue 4, Pages 293-298Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00008571-200106000-00003
Keywords
P-glycoprotein; MDR1; polymorphism; rhodamine 123
Ask authors/readers for more resources
P-glycoprotein (PGP) is a membrane protein which determines drug disposition in humans (e.g. digoxin), It is also expressed in various leukocyte lineages with highest expression in CD56(+) natural killer cells, Recently, a polymorphism in exon 26 (C3435T) of this gene was shown to correlate with intestinal PGP expression and function in humans. Carriers homozygous for this polymorphism (TT) showed more than two-fold lower PGP expression and higher digoxin plasma concentrations compared to the CC group, However, it is not known whether this mutation in the MDR1 gene is also associated with altered PGP function in peripheral blood cells, We therefore assessed efflux of the PGP-substrate rhodamine 123 from CD56(+) natural killer cells, Leukocytes were isolated from whole blood of 10 CC, 10 CT and 11 TT healthy Caucasian individuals, Using flow cytometry, rhodamine fluorescence was determined in CD56(+) cells, Moreover, MDR1 mRNA was quantified in leukocytes by real-time polymerase chain reaction. Subjects with CC genotype revealed a significantly lower rhodamine fluorescence (i.e. higher PGP function) compared to individuals with TT genotype (51.1 +/- 11.4% versus 67.5 +/- 9.5%, p < 0.01), Heterozygous individuals had an intermediate rhodamine fluorescence (61.4 6.3%), MDR1 mRNA normalized for cyclophilin was lowest in the TT population (1.29 +/- 1.01), intermediate in heterozygous subjects (1.60 +/- 0.76) and highest in the CC group (1.91 +/- 0.94; not significant), In summary, subjects being homozygous for C in position 3435 of the MDR1 gene have a more pronounced efflux of rhodamine from CD56(+) natural killer cells and a higher MDRI mRNA expression in leukocytes than subjects with the TT genotype, Measurement of rhodamine efflux using flow-cytometry from peripheral blood cells allows assessment of genetically determined differences in P-glycoprotein function. Pharmacogenetics 11:293-298 (C) 2001 Lippincoit Williams & Wilkins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available