MDR1 polymorphisms G2677T in exon 21 and C3435T in exon 26 fail to affect rhodamine 123 efflux in peripheral blood lymphocytes

被引:60
作者
Oselin, K
Gerloff, T
Mrozikiewicz, PM
Pähkla, R
Roots, I
机构
[1] Humboldt Univ, Inst Clin Pharmacol, Med Ctr Charite, D-10117 Berlin, Germany
[2] Univ Tartu, Inst Pharmacol, EE-51014 Tartu, Estonia
关键词
MDR1 genetic polymorphism; peripheral blood lymphocytes; P-glycoprotein; Rh123; efflux;
D O I
10.1046/j.1472-8206.2003.00163.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:463 / 469
页数:7
相关论文
共 37 条
[31]   Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and response in Jordanian rheumatoid arthritis patients [J].
Samara, Sima A. ;
Irshaid, Yacoub M. ;
Mustafa, Khader N. .
INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, 2014, 52 (09) :746-755
[32]   Association of treatment-resistant schizophrenia with the G2677A/T and C3435T polymorphisms in the ATP-binding cassette subfamily B member 1 gene [J].
Takao, T ;
Tachikawa, H ;
Kawanishi, Y ;
Katano, T ;
Sen, B ;
Homma, M ;
Kohda, Y ;
Mizukami, K ;
Asada, T .
PSYCHIATRIC GENETICS, 2006, 16 (02) :47-48
[33]   Effect of ABCB1 (MDR1) 3435C>T and 2677G>A,T polymorphisms and P-glycoprotein inhibitors on salivary digoxin secretion in congestive heart failure patients [J].
Bartnicka, Lilianna ;
Kurzawski, Mateusz ;
Drozdzik, Agnieszka ;
Plonska-Gosciniak, Edyta ;
Gornik, Wanda ;
Drozdzik, Marek .
PHARMACOLOGICAL REPORTS, 2007, 59 (03) :323-329
[34]   ABCB1 C1236T, G2677TA and C3435T Genetic Polymorphisms and Antidepressant Response Phenotypes: Results from a Portuguese Major Depressive Disorder Cohort [J].
Santos, Marlene ;
Lima, Luis ;
Carvalho, Serafim ;
Brandao, Andreia ;
Barroso, Fatima ;
Cruz, Agostinho ;
Medeiros, Rui .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (10)
[35]   MDR-1 C3435T polymorphism may affect blood pressure in resistant hypertensive patients independently of its effects on aldosterone release [J].
Lacchini, Riccardo ;
Figueiredo, Valeria N. ;
Demacq, Caroline ;
Coeli-Lacchini, Fernanda B. ;
Martins, Luis C. ;
Yugar-Toledo, Juan ;
Coca, Antonio ;
Tanus-Santos, Jose E. ;
Moreno, Heitor, Jr. .
JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, 2014, 15 (02) :170-176
[36]   ABCB1 single nucleotide polymorphisms (1236C > T, 2677G > T, and 3435C > T) do not affect transport activity of human P-glycoprotein [J].
Dickens, David ;
Owen, Andrew ;
Alfirevic, Ana ;
Pirmohamed, Munir .
PHARMACOGENETICS AND GENOMICS, 2013, 23 (06) :314-323
[37]   A correlative study of polymorphisms of CYP2C19 and MDR1 C3435T with the pharmacokinetic profiles of lansoprazole and its main metabolites following single oral administration in healthy adult Chinese subjects [J].
Li, Chang-Yin ;
Zhang, Jun ;
Chu, Ji-Hong ;
Xu, Mei-Juan ;
Ju, Wen-Zheng ;
Liu, Fang ;
Zou, Jian-Dong .
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, 2014, 39 (02) :121-128