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  • 1
    Electronic Resource
    Electronic Resource
    Polymorphisms in Beta-Adrenergic Receptor Genes in the Acquired Long QT Syndrome (2002)
    Oxford, UK : Blackwell Science Inc
    Journal of cardiovascular electrophysiology 13 (2002), S. 0 
    Details
    ISSN: 1540-8167
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Adrenergic Receptor Polymorphism and Arrhythmia. Introduction: Sympathetic activation is a trigger for life-threatening arrhythmias in many patients with the congenital long QT syndrome (LQTS), and an increase in heart rate has been reported just prior to torsades de pointes in patients with drug-associated (acquired) LQTS (aLQTS). We compared the frequencies of five recognized nonsynonymous coding region polymorphisms in genes encoding the β1-adrenergic and β2-adrenergic receptors (AR) in 93 patients with aLQTS and 3 control groups: an ethically diverse set of individuals from middle Tennessee (n = 71), a subset of the Polymorphism Discovery Resource obtained from National Human Genome Research Institute (n = 89), and patients who tolerated QT-prolonging drugs without aLQTS (non-aLQTS group; n = 66). Methods and Results: Polymerase chain reaction-restriction fragment length polymorphism was used to screen for Ser49Gly and Gly389Arg (β1-AR) and Thr164Ile (β2-AR). For Arg16Gly and Gln27Glu, polymorphic sites 33 nucleotides apart in the β2-AR, single-stranded conformational polymorphism was used to distinguish among the 4 possible haplotypes and 10 possible genotypes. Allele frequencies were similar among the 4 groups at the 2β1-AR sites. The uncommon Ile164 variant in β2-AR was slightly more frequent in patients (3.2%) than in any of the 3 control groups (0.6% to 2.3%). At the 16–27 neighboring sites in the β2-AR, one haplotype (Arg16/Glu27) was not detected, as in previous studies; hence, only 6 genotypes were present. There were fewer Gly16/Gln27 homozygotes in the non-aLQTS group (1.5%) than in two other control groups or the aLQTS group (8.5% to 10%). Conclusion: None of the five common nonsynonymous coding region polymorphisms in the β-AR genes predict drug-associated torsades de pointes, although the Gly16/Gln27 haplotype may be a risk factor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1540-8167.2002.00252.x
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  • 2
    Electronic Resource
    Electronic Resource
    MOLECULAR BASIS OF ETHNIC DIFFERENCES IN DRUG DISPOSITION AND RESPONSE (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 41 (2001), S. 815-850 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract Ethnicity is an important demographic variable contributing to interindividual variability in drug metabolism and response. In this rapidly expanding research area many genetic factors that account for the effects of ethnicity on pharmacokinetics, pharmacodynamics, and drug safety have been identified. This review focuses on recent developments that have improved understanding of the molecular mechanisms responsible for such interethnic differences. Genetic variations that may provide a molecular basis for ethnic differences in drug metabolizing enzymes (CYP 2C9, 2C19, 2D6, and 3A4), drug transporter (P-glycoprotein), drug receptors (adrenoceptors), and other functionally important proteins (eNOS and G proteins) are discussed. A better understanding of the molecular basis underlying ethnic differences in drug metabolism, transport, and response will contribute to improved individualization of drug therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.41.1.815
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  • 3
    Electronic Resource
    Electronic Resource
    TRANSPORTERS AND RENAL DRUG ELIMINATION (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 44 (2004), S. 137-166 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Carrier-mediated processes, often referred to as transporters, play key roles in the reabsorption and secretion of many endogenous and xenobiotic compounds by the kidney. The renal proximal tubule is the primary site of active transport for a wide variety of substrates, including organic anions/cations, peptides, and nucleosides. During the past decade, significant advances in molecular identification and characterization of transporter proteins have been made. Although it is generally noted that these transporters significantly contribute to renal drug handling and variability in drug disposition, the extent of our knowledge regarding the specific roles of such transporters in drug disposition and drug-drug interactions remains, for the most part, limited. In this review, we summarize recent progress in terms of molecular and functional characterization of renal transporters and their clinical relevance to drug therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.44.101802.121856
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  • 4
    Electronic Resource
    Electronic Resource
    The orphan nuclear receptor HNF4α determines PXR- and CAR-mediated xenobiotic induction of CYP3A4 (2003)
    [s.l.] : Nature Publishing Group
    Nature medicine 9 (2003), S. 220-224 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is thought to be involved in the metabolism of nearly 50% of all the drugs currently prescribed. Alteration in the activity or expression of this enzyme seems to be a key predictor of drug responsiveness and toxicity. Currently available ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm815
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