Proceedings of the Korea Environmental Mutagen Society Conference (한국환경성돌연변이발암원학회:학술대회논문집)
- 2004.05a
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- Pages.27-29
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- 2004
Genetic Polymorphisms in Drug Transporters and Regulatory Xenobiotic Receptors in Korean Population
- Lee, Sang-Seop (Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine) ;
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Shin, Jae-Gook
(Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine)
- Published : 2004.05.28
Abstract
Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDR1 gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorphisms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.
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