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Gene interactions in pharmacogenomics

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The genetic basis of interindividual differences in drug responses, such as efficacy, dose requirements and adverse events are the focus of pharmacogenomics. Over the past 10 years, since the completion of the Human Genome Project, research in pharmacogenomics has grown and evolved from a candidate-gene ...

The genetic basis of interindividual differences in drug responses, such as efficacy, dose requirements and adverse events are the focus of pharmacogenomics. Over the past 10 years, since the completion of the Human Genome Project, research in pharmacogenomics has grown and evolved from a candidate-gene approach to genome-wide association studies (GWAS). Recently, next-generation sequencing (NGS) technologies aim to identify the possible contribution of genetic polymorphisms with low minor allele frequencies to complex diseases and pharmacogenomics. As drug response phenotypes are multifactorial and multigenic, novel approaches are required to unravel the complex interactions among the multiple genes and the environment, which can be associated to adverse reactions or drug response efficacy.

Regarding candidate-gene approaches to pharmacogenetics, either single-locus or haplotype analyses are mostly conducted in order to test the association of genotypes or the combination of alleles at multiple loci with drug response phenotypes. Importantly, gene-gene interaction analyses considering the genotypes of polymorphisms of different candidate genes within metabolic pathways are also biologically plausible. It is worth to point out that significant association findings must be replicated by studies evaluating different populations with distinct genetic backgrounds. However, contradictory results have been reported regarding gene–gene interactions on pharmacogenomics. Some potential issues responsible for these findings may include the definition of drug response phenotypes, the importance to provide the underlying molecular mechanisms which support the selection of candidate genes, the functional and/or clinical information criteria for the selection of genetic polymorphisms, sample size, among others. Therefore, reviews and commentaries addressing potential issues responsible to contradictory findings on pharmacogenomic studies are welcome at this Frontier Research Topic.

Research contributions on the interactions among gene regulatory elements within promoters and enhancers and transcription factors, which may be unraveled by NGS applications such as chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq), and related to pharmacogenomic traits are also welcome, since they may unravel novel mechanisms underlying the variability of drug response phenotypes.

The overall purpose of this Research Topic will be to gather original articles, reviews and opinions which highlight research on pharmacogenomics, with focus on gene-gene and gene-environment interactions, and on interactions among pharmacogene regulatory elements. Some examples of potential Research Topics include:

• Gene-gene interactions including polymorphisms of candidate genes within metabolic pathways

• Gene-environment interactions on pharmacogenomics

• Clinical relevance of interactions among genetic and environmental factors to pharmacogenomics

• Review and commentaries on the role of epistasis in pharmacogenomics

• Functional role of gene-gene interactions and the definition of predictive pharmacogenomic biomarkers

• NGS applications which may unravel novel variants and mechanisms underlying drug response phenotypes

• Interaction among transcription factors and gene regulatory elements related to pharmacogenomic traits

This Frontiers Research Topic will be an opportunity to pharmacologists, geneticists, and other researchers in order to intensify collaborations.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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