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Review
. 2016 Oct;14(5):298-313.
doi: 10.1016/j.gpb.2016.03.008. Epub 2016 Oct 8.

Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine

Shabbir Ahmed  1 , Zhan Zhou  1 , Jie Zhou  1 , Shu-Qing Chen  2
Affiliations
Review

Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine

Shabbir Ahmed et al. Genomics Proteomics Bioinformatics. 2016 Oct.

Erratum in

Abstract

The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual's particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pharmacogenomics of phase-I drug metabolizing enzymes and transporters. Substantial frequency differences in key variants of drug metabolizing enzymes and transporters, as well as their possible functional consequences, have also been discussed across geographic regions. The current effort illustrates the common presence of variability in drug responses among individuals and across all geographic regions. This information will aid health-care professionals in prescribing the most appropriate treatment aimed at achieving the best possible beneficial outcomes while avoiding unwanted effects for a particular patient.

Keywords: Drug transporters; Genetic polymorphism; Pharmacogenomics; Phase-I drug-metabolizing enzymes; Precision medicine.

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Figures

Figure 1
Figure 1
Effect of genetic polymorphisms on individuals’ drug response Pharmacokinetics and pharmacodynamics are main determinants of interindividual differences in drug responses. Genetic polymorphism in genes related to these processes may result in mild to severe variations in drug responses. ADRs, adverse drug reactions.
Figure 2
Figure 2
An overview of important consequences of genetic polymorphisms in the CYPs Overview of the effect of genetic polymorphisms on some human cytochrome P450 variant alleles and molecular mechanisms leading to altered drug metabolism.
Figure 3
Figure 3
The influence of genetic polymorphisms of ABC transporters on the drug transport activities The diagram depicts the influence of genetic polymorphisms on the drug transport activities of ABC transporters. ABC transporter, ATP-binding cassette transporter; MDR1, multidrug resistance protein 1; BCRP, breast cancer resistance protein; MRP, multidrug resistance-associated protein.
Figure 4
Figure 4
Modification of drug transport activities of SLC transporters by genetic polymorphisms The diagram depicts the influence of genetic polymorphisms on the transport activities of different allele variants of SLC transporters including SLCO and SLC47 (A) as well as SLC22 (B). SLC, solute carrier; SLCO, solute carrier organic anion; OCT, organic cation transporter; OCTN, organic cation transporter novel; OAT, organic anion transporter; MATE1, multidrug and toxin extrusion protein 1; URAT, urate transporter.
See this image and copyright information in PMC

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