About this Research Topic
With conventional treatment strategy, up to 50% of patients experience poor drug response or adverse drug reactions. Importantly, 20-30% of this variability can be attributed to genetic factors, i.e. variations in genes that are involved in drug absorption, distribution, metabolism and excretion (ADME), in genes that encode drug targets, or in human leukocyte antigen (HLA) genes that are related to immune activation. Over the last few decades, the advance of next generation sequencing technologies has allowed for the identification of variants in pharmacogenes with high speed and minimized cost. This led to the identification of remarkable differences in prevalence, i.e. allele frequencies of pharmacogenetic variants, and their exploration at the population level. In particular, the extensive variability of Cytochrome P450 (CYP) genes, such as CYP2D6, has been reported across European countries as well as on a global scale.
Inter-ethnic phenotypic differences can be largely explained by genetic variations. Some geographically isolated populations possess unique genetic structures with population-specific founder mutations and are likely to have distinct pharmacogenomic profiles. While a vast number of correlations between genotypes and abnormal drug responses have been discovered, it is utmost importance to establish reliable pharmacogenomic biomarkers on a population scale, which hold promise to improve country-specific precision public health care strategies. Furthermore, to facilitate the implementation of Population pharmacogenomics (PGx) in routine clinical care, cost-effectiveness of preemptive genotyping strategies needs to be assessed with the incorporation of country-specific socioeconomic metrics, particularly for biomarkers that are associated with severe adverse drug reactions. A typical example would be the presence of the variant HLA-B*15:02 in Asian populations, which has an allele frequency up to 22% and leads to the potential development of Stevens-Johnson syndrome/toxic epidermal necrolysis in carriers who take carbamazepine. The preemptive genotyping of HLA-B*15:02 has been demonstrated to be cost-effective and included in the guidelines of both U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Additionally, population considerate PGx plays an important role in drug development.
The pharmacogenomic biomarker-enriched randomized clinical trials could guide the drug development process to maximize the drug efficacy and minimize the Adverse Drug Reactions (ADRs) for patients from diverse ancestral and geographical backgrounds. Overall, studies on aforementioned aspects of population PGx will benefit both public health and genome-oriented drug development, particularly for understudied countries/ethnicities and countries with diverse ethnicities. The overall purpose of this Research Topic will be to gather Original Research articles, Reviews and Opinion pieces, which focus on population-specific pharmacogenomic variant discovery, interpretation and implementation in clinical care, and drug development.
Topic Editors acknowledge Mr. Yitian Zhou for his valuable contribution in the design and finalization of this Research Topic proposal.
Topic Editor Prof. Volker M. Lauschke is co-founder and shareholder of HepaPredict AB
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