Dataset Information

Polymorphisms in genes involved in the absorption, distribution, metabolism, and excretion of drugs in the Kazakhs of Kazakhstan.

ABSTRACT: Studies of genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are crucial to the development of therapeutics in clinical medicine. Such data provide information that may improve our understanding of individual differences in sensitivity or resistance to certain drugs, thereby helping to avoid adverse drug reactions (ADRs) in patients and improve the quality of therapies. Here, we aimed to analyse single nucleotide polymorphisms (SNPs) involved in the ADME of multiple drugs in Kazakhs from Kazakhstan.A total of 158 SNPs involved in the ADME of various drugs were studied. We analysed 320 Kazakh DNA samples using OpenArray genotyping. Of the 158 SNPs, 75 were not found in heterozygous or homozygous variants. Comparative analysis among Kazakhs and world populations showed a fairly high percentage of population differentiation.These results provide further information for pharmacogenetic databases and may contribute to the development of personalized approaches and safer therapies for the Kazakh population. Moreover, these data provide insights into the different racial groups that may have contributed to the Kazakh population.

SUBMITTER: Iskakova AN

PROVIDER: S-EPMC4717528 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Polymorphisms in genes involved in the absorption, distribution, metabolism, and excretion of drugs in the Kazakhs of Kazakhstan.

Iskakova Aisha N AN Romanova Aliya A AA Aitkulova Akbota M AM Sikhayeva Nurgul S NS Zholdybayeva Elena V EV Ramanculov Erlan M EM

BMC genetics 20160119

<h4>Background</h4>Studies of genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are crucial to the development of therapeutics in clinical medicine. Such data provide information that may improve our understanding of individual differences in sensitivity or resistance to certain drugs, thereby helping to avoid adverse drug reactions (ADRs) in patients and improve the quality of therapies. Here, we aimed to analyse single nucleotide polymorphisms (SNPs) inv ...[more]

PMID: 26785747

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Project description:A reliable translation of in vitro and preclinical data on drug absorption, distribution, metabolism, and excretion (ADME) to humans is important for safe and effective drug development. Precision medicine that is expected to provide the right clinical dose for the right patient at the right time requires a comprehensive understanding of population factors affecting drug disposition and response. Characterization of drug-metabolizing enzymes and transporters for the protein abundance and their interindividual as well as differential tissue and cross-species variabilities is important for translational ADME and precision medicine. This review first provides a brief overview of quantitative proteomics principles including liquid chromatography-tandem mass spectrometry tools, data acquisition approaches, proteomics sample preparation techniques, and quality controls for ensuring rigor and reproducibility in protein quantification data. Then, potential applications of quantitative proteomics in the translation of in vitro and preclinical data as well as prediction of interindividual variability are discussed in detail with tabulated examples. The applications of quantitative proteomics data in physiologically based pharmacokinetic modeling for ADME prediction are discussed with representative case examples. Finally, various considerations for reliable quantitative proteomics analysis for translational ADME and precision medicine and the future directions are discussed. SIGNIFICANCE STATEMENT: Quantitative proteomics analysis of drug-metabolizing enzymes and transporters in humans and preclinical species provides key physiological information that assists in the translation of in vitro and preclinical data to humans. This review provides the principles and applications of quantitative proteomics in characterizing in vitro, ex vivo, and preclinical models for translational research and interindividual variability prediction. Integration of these data into physiologically based pharmacokinetic modeling is proving to be critical for safe, effective, timely, and cost-effective drug development.

Dataset Information

Polymorphisms in genes involved in the absorption, distribution, metabolism, and excretion of drugs in the Kazakhs of Kazakhstan.

Publications

Polymorphisms in genes involved in the absorption, distribution, metabolism, and excretion of drugs in the Kazakhs of Kazakhstan.

Similar Datasets

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