Due to the major role of mitochondrial dysfunction in the onset of adverse drug reactions, it has been hypothesized that variation in mtDNA may underpin some of the idiosyncrasies associated with drug-induced toxicity by offering another source of inter-individual variation. Many studies cite evidence to suggest that there is a link between inter-individual mtDNA variation and some forms of drug-induced adverse drug reactions, importantly, including those which are unpredictable. So far, however, its importance to the clinical setting remains unclear due to limitations in study design, particularly size and genotypic diversity. However, the rapid advances in both the understanding of mitochondrial genetics and the technology with which to investigate it present exciting opportunities to further establish mitochondrial genotype as an important topic in the study of pharmacogenomics, drug development, and translational drug safety.
Recent publications suggest that in most cases, susceptibility cannot be explained by defining macro haplogroup associations alone. For example, specific mtDNA mutations that may be determinants for some adverse drug reactions can be found in multiple sub-haplogroups, in addition to the presence of haplogroup-specific nuclear DNA interactions or nuclear-modifier genes that alter the phenotype of the mtDNA variant. The rapid advancements in whole-genome sequencing technologies present the opportunity to understand more clearly how important individual mtDNA variation in the onset of toxicity. In addition, functional studies, in particular utilizing primary tissue and/or transmitochondrial cybrids, presents the opportunity to elucidate the mechanisms linking specific single nucleotide polymorphisms, or a pattern of such polymorphisms, with toxicity.
We will accept original research manuscripts reporting on the investigation of the role of mtDNA in any aspect of drug-induced toxicity and adverse drug reactions. These can be the results of retrospective or prospective clinical trials working with patient cohorts, or functional studies utilizing in vitro or ex vivo model systems.
Due to the major role of mitochondrial dysfunction in the onset of adverse drug reactions, it has been hypothesized that variation in mtDNA may underpin some of the idiosyncrasies associated with drug-induced toxicity by offering another source of inter-individual variation. Many studies cite evidence to suggest that there is a link between inter-individual mtDNA variation and some forms of drug-induced adverse drug reactions, importantly, including those which are unpredictable. So far, however, its importance to the clinical setting remains unclear due to limitations in study design, particularly size and genotypic diversity. However, the rapid advances in both the understanding of mitochondrial genetics and the technology with which to investigate it present exciting opportunities to further establish mitochondrial genotype as an important topic in the study of pharmacogenomics, drug development, and translational drug safety.
Recent publications suggest that in most cases, susceptibility cannot be explained by defining macro haplogroup associations alone. For example, specific mtDNA mutations that may be determinants for some adverse drug reactions can be found in multiple sub-haplogroups, in addition to the presence of haplogroup-specific nuclear DNA interactions or nuclear-modifier genes that alter the phenotype of the mtDNA variant. The rapid advancements in whole-genome sequencing technologies present the opportunity to understand more clearly how important individual mtDNA variation in the onset of toxicity. In addition, functional studies, in particular utilizing primary tissue and/or transmitochondrial cybrids, presents the opportunity to elucidate the mechanisms linking specific single nucleotide polymorphisms, or a pattern of such polymorphisms, with toxicity.
We will accept original research manuscripts reporting on the investigation of the role of mtDNA in any aspect of drug-induced toxicity and adverse drug reactions. These can be the results of retrospective or prospective clinical trials working with patient cohorts, or functional studies utilizing in vitro or ex vivo model systems.
