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New assay identifies SNPs in the MDR1 gene: implications for individualized drug therapies
By Sharon Guynup

German researchers have developed a new assay for identifying single nucleotide polymorphisms (SNPs) within the MDR1 gene. The product of MDR1, P-glycoprotein, regulates the bioavailability and effectiveness of a number of common drugs, such as the heart medication digoxin. One polymorphism, which was found in more than half of the study participants, could affect drug absorption in the gut.

MDR1 polymorphisms can create changes that affect the quantity of P-glycoprotein or alter its function. These changes can limit the effectiveness of drug treatment, or create drug resistance or toxicity. For example, overexpression of P-glycoprotein in tumor cells creates drug resistance to a number of tumor-suppressing drugs. Determining which SNPs a person carries may eventually help doctors prescribe more individualized, and thus more effective, drug treatments for a range of illnesses.

The team studied the frequency of SNPs in the major MDR1 alleles in 461 German volunteers. Of the 15 SNPs identified, most had no effect on protein sequence, but a silent polymorphism in exon 26 was linked to levels of P-glycoprotein in the intestine.

Nearly half of the volunteers carried at least one copy of the exon 26 polymorphism, which decreases the expression of the protein in the intestine. The researchers suggest that the exon 26 polymorphism could seriously affect drug absorption in the gut thus requiring higher doses of some therapies.

Identifying such polymorphisms may aid the individualization of drug treatment, drug design, and increase drug safety.

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Cascorbi, I. et al. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 69, 169-174 (March 2001).

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