期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 102, 期 4, 页码 688-700出版社
WILEY
DOI: 10.1002/cpt.690
关键词
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资金
- European Union [668353]
- Swedish Research Council [2015-02760, 2016-01153, 2016-01154]
- Swedish Research Council [2015-02760] Funding Source: Swedish Research Council
Genetic polymorphisms in cytochrome P450 (CYP) genes can result in altered metabolic activity toward a plethora of clinically important medications. Thus, single nucleotide variants and copy number variations in CYP genes are major determinants of drug pharmacokinetics and toxicity and constitute pharmacogenetic biomarkers for drug dosing, efficacy, and safety. Strikingly, the distribution of CYP alleles differs considerably between populations with important implications for personalized drug therapy and healthcare programs. To provide a global distribution map of CYP alleles with clinical importance, we integrated whole-genome and exome sequencing data from 56,945 unrelated individuals of five major human populations. By combining this dataset with population-specific linkage information, we derive the frequencies of 176 CYP haplotypes, providing an extensive resource for major genetic determinants of drug metabolism. Furthermore, we aggregated this dataset into spectra of predicted functional variability in the respective populations and discuss the implications for population-adjusted pharmacological treatment strategies.
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