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Influence of Development, HIV Infection, and Antiretroviral Therapies on the Gene Expression Profiles of ABC Transporters in Human Lymphocytes
Author(s) -
Giraud Carole,
Manceau Sandra,
Declèves Xavier,
Goffinet François,
Morini JeanPierre,
Chappuy Hélène,
Batteux Frédéric,
Chouzenoux Sandrine,
Scherrmann JeanMichel,
Blanche Stéphane,
Tréluyer JeanMarc
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009343696
Subject(s) - transporter , atp binding cassette transporter , efflux , gene expression , biology , gene , pharmacology , zidovudine , intracellular , human immunodeficiency virus (hiv) , immunology , medicine , genetics , viral disease
The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive, and antiretroviral drugs depends on their intracellular concentrations, which could be modulated by membrane efflux pumps belonging to the ABC transporter superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1, MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV‐infected, respectively). Gene expression levels were quantified by quantitative RT‐PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5 gene. BCRP and MRP4 genes were significantly higher expressed at birth than after 1 month of life. Neither HIV infection nor antiretroviral therapies modulated the gene expression profiles of ABC transporters. In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns.