Abstract:
:Acetaminophen (APAP) is widely used as an over-the-counter fever reducer and pain reliever. However, the current therapeutic use of APAP is not optimal. The inter-patient variability in both efficacy and toxicity limits the use of this drug. This is particularly an issue in pediatric populations, where tools for predicting drug efficacy and developmental toxicity are not well established. Variability in toxicity between age groups may be accounted for by differences in metabolism, transport, and the genetics behind those differences. While pharmacogenomics has been revolutionizing the paradigm of pharmacotherapy for many drugs, its application in pediatric populations faces significant challenges given the dynamic ontogenic changes in cellular and systems physiology. In this review we focused on the ontogenesis of the regulatory pathways involved in the disposition of APAP and on the variability between pediatric, adolescent, and adult patients. We also summarize important polymorphisms of the pharmacogenes associated with APAP metabolism. Pharmacogenetic studies in pediatric APAP treatment are also reviewed. We conclude that while a consensus in pharmacogenetic management of APAP in pediatric populations has not been achieved, a systems biology based strategy for comprehensively understanding the ontogenic regulatory pathway as well as the interaction between age and genetic variations are particularly necessary in order to address this question.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Krasniak AE,Knipp GT,Svensson CK,Liu Wdoi
10.3389/fgene.2014.00314subject
Has Abstractpub_date
2014-10-14 00:00:00pages
314issn
1664-8021journal_volume
5pub_type
杂志文章,评审abstract::Cell viability and gene expression profiles are altered in cellular models of neurodegenerative disorders such as Huntington's Disease (HD). Using the yeast model system, we show that the SUMO-targeted ubiquitin ligase (STUbL) Slx5 reduces the toxicity and abnormal transcriptional activity associated with a mutant, ag...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00379
更新日期:2018-09-18 00:00:00
abstract::Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia with a highly heterogeneous genetic background; it usually occurs in infancy. Approximately 30-40% of patients have other associated congenital anomalies; in particular, facial anomalies, such as cleft palate, are part of about 10% of the DBA clinica...
journal_title:Frontiers in genetics
pub_type:
doi:10.3389/fgene.2018.00549
更新日期:2018-11-19 00:00:00
abstract::This study assessed the accuracy and bias of genomic prediction (GP) in purebred Holstein (H) and Jersey (J) as well as crossbred (H and J) validation cows using different reference sets and prediction strategies. The reference sets were made up of different combinations of 36,695 H and J purebreds and crossbreds. Add...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.598580
更新日期:2020-12-14 00:00:00
abstract::Ionizing radiation (IR) is a high-energy radiation whose biological effects depend on the irradiation doses. Low-dose radiation (LDR) is delivered during medical diagnoses or by an exposure to radioactive elements and has been linked to the occurrence of chronic diseases, such as leukemia and cardiovascular diseases. ...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2020.566244
更新日期:2020-10-02 00:00:00
abstract::Glioblastoma, also called glioblastoma multiform (GBM), is the most aggressive cancer that initiates within the brain. GBM is produced in the central nervous system. Cancer cells in GBM are similar to stem cells. Several different schemes for GBM stratification exist. These schemes are based on intertumoral molecular ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.604336
更新日期:2020-11-24 00:00:00
abstract::Circadian rhythms produce a biological measure of the time of day. In plants, circadian regulation forms an essential adaptation to the fluctuating environment. Most of our knowledge of the molecular aspects of circadian regulation in plants is derived from laboratory experiments that are performed under controlled co...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.01239
更新日期:2019-11-29 00:00:00
abstract::Neurodegenerative diseases share pathogenic mechanisms at the cellular level including protein misfolding, excitotoxicity and altered RNA homeostasis among others. Recent advances have shown that the genetic causes underlying these pathologies overlap, hinting at the existence of a genetic network for neurodegeneratio...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2014.00085
更新日期:2014-04-17 00:00:00
abstract::The goal of this work was to determine the effect of nonablative syngeneic transplantation of young bone marrow (BM) to laboratory animals (mice) of advanced age upon maximum duration of their lifespan. To do this, transplantation of 100 million nucleated cells from BM of young syngeneic donors to an old nonablated an...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00310
更新日期:2019-04-12 00:00:00
abstract::Staphylococcus epidermidis is one of the most commonly isolated species from human skin and the second leading cause of bloodstream infections. Here, we performed a large-scale comparative study without any pre-assigned reference to identify genomic determinants associated with the diversity and adaptation of S. epide...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.566080
更新日期:2020-11-09 00:00:00
abstract::Predicting how species interactions evolve requires that we understand the mechanistic basis of coevolution, and thus the functional genotype-by-genotype interactions (G × G) that drive reciprocal natural selection. Theory on host-parasite coevolution provides testable hypotheses for empiricists, but depends upon mode...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00077
更新日期:2014-04-11 00:00:00
abstract::Posttraumatic Stress Disorder (PTSD) is a complex illness, frequently co-morbid with depression, caused by both genetics, and the environment. Alcohol Use Disorder (AUD), which also co-occurs with depression, is often co-morbid with PTSD. To date, very few genes have been identified for PTSD and even less for PTSD com...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00566
更新日期:2018-11-27 00:00:00
abstract::Reliability of genomic selection (GS) models was tested in an admixed population of Atlantic salmon, originating from crossing of several wild subpopulations. The models included ordinary genomic BLUP models (GBLUP), using genome-wide SNP markers of varying densities (1-220 k), a genomic identity-by-descent model (IBD...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00402
更新日期:2014-11-21 00:00:00
abstract::Muscle weakness is a common consequence of both aging (sarcopenia) and neuromuscular disorders (NMD). Whilst genome-wide association (GWA) studies have identified genetic variants associated with grip strength (GS; measure of muscle strength/weakness) and NMDs, including multiple sclerosis (MS), myasthenia gravis (MG)...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00393
更新日期:2020-04-24 00:00:00
abstract::Background: Alcohol use has been linked to a number of physical conditions, but the relationship between alcohol drinking and depression, one of the most common mental disorders that is a significant contributor to the global burden of disease, is still under debate. We aim to help fill the literature gap on the causa...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.585351
更新日期:2020-10-19 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is generally incurable due to the late diagnosis and absence of markers that are concordant with expression in several sample sources (i.e., tissue, blood, plasma) and platforms (i.e., Microarray, sequencing). We optimized meta-analysis of 19 PDAC (tissue and blood) transcriptom...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.572284
更新日期:2020-09-10 00:00:00
abstract::The sustainable development of aquaculture has been impeded by infectious diseases worldwide. However, the genomic architecture and the genetic basis underlying the disease resistance remain poorly understood, which severely hampers both the understanding of the evolution of fish disease resistance traits and the prev...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.01167
更新日期:2019-11-20 00:00:00
abstract::Objective: Adrenocortical carcinoma (ACC) is a rare but aggressive malignant cancer that has been attracting growing attention over recent decades. This study aims to integrate protein interaction networks with gene expression profiles to identify potential biomarkers with prognostic value in silico. Methods: Three mi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00821
更新日期:2019-09-11 00:00:00
abstract::Brugada syndrome (BrS) is a heritable disease that results in sudden cardiac death. In the exome/genomic era, certain reported pathogenic variants in some genetic diseases have been reclassified as benign owing to their high frequency in some ancestries. In the present study, we comprehensively reassessed all previous...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00680
更新日期:2019-01-04 00:00:00
abstract::In animals, interactions among gene products of mitochondrial and nuclear genomes (mitonuclear interactions) are of profound fitness, evolutionary, and ecological significance. Most fundamentally, the oxidative phosphorylation (OXPHOS) complexes responsible for cellular bioenergetics are formed by the direct interacti...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2017.00025
更新日期:2017-03-03 00:00:00
abstract::Bamboo is one of the fastest-growing non-timber forest plants. Moso bamboo (Phyllostachys edulis) is the most economically valuable bamboo in Asia, especially in China. With the release of the whole-genome sequence of moso bamboo, there are increasing demands for refined annotation of bamboo genes. Recently, large amo...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00574
更新日期:2018-11-27 00:00:00
abstract::Livestock conservation practice is changing rapidly in light of policy developments, climate change and diversifying market demands. The last decade has seen a step change in technology and analytical approaches available to define, manage and conserve Farm Animal Genomic Resources (FAnGR). However, these rapid change...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2015.00314
更新日期:2015-10-21 00:00:00
abstract::Nutrition is the most important environmental factor that can influence early developmental processes through regulation of epigenetic mechanisms during pregnancy and neonatal periods. Maternal diets or nutritional compositions contribute to the establishment of the epigenetic profiles in the fetus that have a profoun...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2018.00342
更新日期:2018-08-27 00:00:00
abstract::Motivation:Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. Nevertheless, the system is not yet fully understood, although many mechanisms are described, and information for many processes exists. However, the combination and interpre...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2017.00085
更新日期:2017-06-30 00:00:00
abstract::Tumor-infiltrating T-lymphocytes are defined as T-lymphocytes that infiltrated into tumor tissues; however, their composition, clinical significance, and underlying mechanism in hepatocellular carcinoma (HCC) and adjacent non-tumor tissues are still not completely understood. Herein, we collected marker genes of T cel...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.586415
更新日期:2020-09-30 00:00:00
abstract::Purpose: The present study examines the role of Sox11 in the initial response of retinal ganglion cells (RGCs) to axon damage and in optic nerve regeneration in mouse. Methods: Markers of retinal injury were identified using the normal retina database and optic nerve crush (ONC) database on GeneNetwork2 (www.genenetwo...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00633
更新日期:2018-12-18 00:00:00
abstract::Sertoli cells are central and essential coordinators of spermatogenesis. Accumulating evidence has demonstrated that miRNAs participate in the regulation of Sertoli cell growth. However, the functions and the regulatory mechanisms of miRNAs in Sertoli cells of domestic animals remain largely unknown. Here we report th...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.581593
更新日期:2020-10-29 00:00:00
abstract::Chemicals, toxicants, and environmental stressors mediate their biologic effect through specific modes of action (MOAs). These encompass key molecular events that lead to changes in the expression of genes within regulatory pathways. Elucidating shared biologic processes and overlapping gene networks will help to bett...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2017.00157
更新日期:2017-10-24 00:00:00
abstract::Zeng et al. (2005) proposed a general two-allele (G2A) model to model bi-allelic quantitative trait loci (QTL). Comparing with the classical Fisher model, the G2A model can avoid using redundant parameters and be fitted directly using standard least square (LS) approach. In this study, we further extend the G2A model ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00328
更新日期:2014-09-25 00:00:00
abstract::Cytotoxicity assays of immortalized lymphoblastoid cell lines (LCLs) represent a promising new in vitro approach in pharmacogenomics research. However, previous studies employing LCLs in gene mapping have used simple association methods, which may not adequately capture the true differences in non-linear response prof...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2011.00086
更新日期:2011-12-14 00:00:00
abstract::Extracting inherent valuable knowledge from omics big data remains as a daunting problem in bioinformatics and computational biology. Deep learning, as an emerging branch from machine learning, has exhibited unprecedented performance in quite a few applications from academia and industry. We highlight the difference a...
journal_title:Frontiers in genetics
pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.00214
更新日期:2019-03-26 00:00:00