Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Multi Drug Resistance (ABCB1, MDR1) [T88.7]

OMIM number: 171050 (ABCB1)

Dipl.-Biol. Birgit Busse

Scientific Background

The ABCB1 (MDR1) gene encodes for what is called the P-glycoprotein (PGP), which is an integral part of the cell membrane and regulates the energy dependant transport of substrates out of the cell. This process protects the cell from toxic substances. In the intestine it controls the resorption of substances, while in the vascular endothelium the permeability of the blood-brain barrier is regulated. Many drugs (e.g antibiotics, protease inhibitors) are PGP substrates.

The polymorphism c.3435C>T in exon 26 of the ABCB1 gene correlates with the gene expression and therefore with the amount of PGP. A high expression (C/C allele) in the intestine results in a reduced absorption of the drug in the bloodstream, while a low PGP expression (T/T variant) is associated with a higher absorption of the drug. The clinical relevance of polymorphisms in the ABCB1 gene is discussed controversially in the literature. There is evidence that the above-mentioned polymorphism leads to a change in substrate specificity. Furthermore, induction and inhibition by drugs, phytopharmaceuticals and diet play a major role in PGP expression which may alter the transport capacity of substrates.