Functional Polymorphisms of Xenobiotics Metabolizing Enzymes (XME)

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Background

The human genome harbours an impressive number of genes encoding enzymes that primarily metabolize drugs or other xenobiotics. Genetic and functional variation in these genes is tremendous and has complex consequences, depending, for example, on whether enzyme structure or expression is affected, or whether the produced metabolite is pharmacologically or toxicologically active or not. Despite numerous impressive examples of the impact of genetic variation on pharmacokinetics and drug response, today’s knowledge is incomplete regarding most XME genes and fragmentary even for many well-investigated XMEs. This is one of the reasons why clinical pharmacogenetic studies are often controversial and clinical application in personalized medicine is presently limited. Advanced technology and ongoing large-scale projects are rapidly uncovering the existing genetic variation in all populations on earth, ultimately enabling the personal genome in the very near future. A wealth of mostly rare novel variants is awaiting functional characterization either by high-throughput expression/phenotyping techniques or by prediction using improved algorithms to estimate functional relevance.
With this Research Topic we would like to give an up-to-date overview about the current knowledge in this field by covering both, known hard facts as well as cutting-edge advancement in novel genetic and genomic variation of XMEs and their functional consequences. The scope of this Research Topic therefore includes all related areas of experimental research, methodology, modeling and simulation, opinion and strategy, as well as historical or topical review. We encourage the submission of manuscripts. For illustration, some examples of potential Research Topics are given here, but the following list is not comprehensive:
• Novel prediction algorithms for functional effect of SNPs
• Novel structure comparison of amino acid variants with functional implication
• High-throughput method for recombinant expression and functional analysis
• Novel SNPs in XME gene and their functional relevance
• Interethnic and intraethnic variability of XME gene variants
• In vitro / in vivo comparison of phenotypic SNP effects
• Tissue-based genotype-phenotype or genotype/expression correlation analysis
• Substrate-dependent effects of genetic variants
• Identification of causal mutation or functional comparison of haplotypes
• Phenotypic effects of SNPs in non-coding (intronic, silent, 5’- 3’-) areas
• Relevance of microRNA polymorphisms for expression
• Toxicological relevance of XME gene variants
• Metabonomic relevance of XME gene variants
• XME Polymorphisms in animals
• Strategies on exploitation of 1000-genomes project data
• Protocol for XME gene-enrichment for next-generation-sequencing
• RNAseq approaches to dissect splice variants
• Review articles on history and current knowledge of particular gene or group of genes
This Research Topic will be of great interest to pharmacologists, toxicologists and geneticists around the world in order to improve their evidence-based pharmacogenetic strategies, extend the panel of functional and causal variants, and thus improve the benefit of complex and expensive clinical studies. Frontiers Research Topics are a fantastic opportunity to bring your research area to critical mass and to intensify collaborations. All Research Topic articles are freely available on the Internet and submitted to PubMed Central and other archiving facilities.

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