MDR1 polymorphisms G2677T in exon 21 and C3435T in exon 26 fail to affect rhodamine 123 efflux in peripheral blood lymphocytes.
P-glycoprotein (Pgp) is a member of the ABC-transporter family, and in humans, is encoded by the MDR1 gene. Recently, several single-nucleotide polymorphisms in the MDR1 gene were identified. The aim of the present study was to evaluate the effect of the MDR1 genetic polymorphisms G2677T and C3435T on Pgp activity in CD56+ and CD4+ peripheral blood cells. Using flow cytometry, rhodamine 123 (Rh123) efflux was determined in 46 male healthy volunteers. Median Rh123 fluorescence in control sample, after baseline dye uptake, was set as 100%. Rh123 fluorescence in efflux samples, exposed to different efflux periods, was used to calculate the percentage of Rh123 retained in the cells in comparison with control. There was no significant difference in Rh123 efflux in CD56+ cells after 5, 10, 15, and 30 min efflux between individuals with different MDR1 genotypes. Also, in CD4+ cells after 15, 30, 60, and 90 min, Rh123 efflux did not reveal statistically different results for the three genotypes at 2677 and 3435. Rh123 efflux was not enhanced by a 10-day rifampin administration, as determined in 15 individuals before and after rifampin treatment. In conclusion, we found no impact of the MDR1 G2677T and C3435T polymorphisms on Pgp activity in CD56+ and CD4+ peripheral blood lymphocytes.
Oselin
Kersti
K
Institute of Clinical Pharmacology, University Medical Centre Charité, Humboldt University, Schumannstrasse 20/21, D-10117, Berlin, Germany. kersti.oselin@ut.ee
Gerloff
Thomas
T
Mrozikiewicz
Przemyslaw M
PM
Pähkla
Rein
R
Roots
Ivar
I
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D005091:Exons; D019450:Genes, MDR; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020112:Rhodamine 123 / Q000378:metabolism*; D012293:Rifampin / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015704:CD4 Antigens; D019002:CD56 Antigen; D020112:Rhodamine 123; D014700:Verapamil; D012293:Rifampin