Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA312609 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10-8), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.
2016-02-19 | GSE78098 | GEO
Project description:To determine the differential miRNA levels in heroin addicts, we comparatively profiled plasma miRNA expression of heroin abusers and healthy controls using Agilent Human miRNA Array.
2020-10-29 | GSE160275 | GEO
Project description:This a model from the article:
Population-based analysis of methadone distribution and metabolism using an
age-dependent physiologically based pharmacokinetic model.
Yang F, Tong X, McCarver DG, Hines RN, Beard DA. J Pharmacokinet Pharmacodyn
2006 Aug;33(4):485-518 16758333
,
Abstract:
Limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to use
in methadone dosing recommendations in pediatric patients for either opioid
abstinence or analgesia. Considering the extreme inter-individual variability of
absorption and metabolism of methadone, population-based PK would be useful to
provide insight into the relationship between dose, blood concentrations, and
clinical effects of methadone. To address this need, an age-dependent
physiologically based pharmacokinetic (PBPK) model has been constructed to
systematically study methadone metabolism and PK. The model will facilitate the
design of cost-effective studies that will evaluate methadone PK and PD
relationships, and may be useful to guide methadone dosing in children. The PBPK
model, which includes whole-body multi-organ distribution, plasma protein
binding, metabolism, and clearance, is parameterized based on a database of
pediatric PK parameters and data collected from clinical experiments. The model
is further tailored and verified based on PK data from individual adults, then
scaled appropriately to apply to children aged 0-24 months. Based on measured
variability in CYP3A enzyme expression levels and plasma orosomucoid (ORM2)
concentrations, a Monte-Carlo-based simulation of methadone kinetics in a
pediatric population was performed. The simulation predicts extreme variability
in plasma concentrations and clearance kinetics for methadone in the pediatric
population, based on standard dosing protocols. In addition, it is shown that
when doses are designed for individuals based on prior protein expression
information, inter-individual variability in methadone kinetics may be greatly
reduced.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Yang F, Tong X, McCarver DG, Hines RN, Beard DA. (2006) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230040 | BioModels
Project description:SNP profiles from 30 pheochromocytomas and paragangliomas were analyzed to detect identical-by-descent haplotypes, highlighting a founder mutation of SDHD in two samples.
2012-03-23 | GSE32204 | GEO
Project description:Expansion of the hexanucleotide repeat (HR) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Caucasians. All C9orf72 ALS/FTD patients share a common risk (R) haplotype, but its single nucleotide polymorphism (SNP) signature has not been fully characterized. Here, we characterized the C9orf72 haplotypes in Europeans and created a detailed molecular map, including HR length, for each haplotype. By analyzing RNA-seq reads and sequencing chromatograms that overlap with heterozygous SNP sites, we identified allelic differences in C9orf72 expression in normal subjects and ALS patients. In cells from healthy individuals, upstream promoter transcript levels increased with increased HR length. Intron 1 levels were higher in one of the non-R haplotypes due to SNP variation, and in R haplotype with 10 or more HR units. In pathological HR expansion, we observed the highest levels of intron 1 that were accompanied by aberrantly spliced transcripts at cryptic donor sites downstream of the expanded HR. Intron 1 retention was associated with sequential intron 2 retention. The SNP signature of C9orf72 haplotypes described here enables allele-specific analysis of transcriptional products and may pave the way to allele-specific therapeutic strategies.
2021-03-01 | GSE162943 | GEO
Project description:SNP profiles from 30 pheochromocytomas and paragangliomas were analyzed to detect identical-by-descent haplotypes, highlighting a founder mutation of SDHD in two samples. 30 pheochromocytomas and paragangliomas were analyzed with Illumina Human610-Quad v1.0 BeadChips.
2012-03-23 | E-GEOD-32204 | biostudies-arrayexpress
Project description:This is a prospective, clinical study. This study is to evaluate the sensitivity of plasma ctDNA methylation haplotypes in detecting local residual or lymph node metastasis.
| 2299281 | ecrin-mdr-crc
Project description:Several studies have investigated changes induced by drug exposure, but few reports have described changes that persist following relapse. In the present study, genome-wide analysis of gene expression was conducted in rats that expressed behavioral incubation of heroin-seeking and goal-directed behavior. The medial prefrontal cortex (mPFC) is important in mediating goal-directed behavior and also was the target of this analysis. Rats were trained to self-administer heroin (0.06 mg/0.2 ml infusion) during 3 hour daily sessions for 14 days. Following the self-administration period, rats were reintroduced to the self-administration chambers for a 90-minute extinction session. The extinction session occurred either 1 day or 14 days following the final self-administration session. Behavioral data demonstrated incubation (increased expression) of heroin-seeking and goal-directed behavior after the 14 day abstinent period. Whole genome analysis was performed and selected results were confirmed by quantitative real-time PCR (RT-qPCR). Microarrays identified 66 genes whose expression was identified as changed by at least 1.4 fold (p<0.02) following 14 days of abstinence and the 90-minute extinction session, and seven of the genes on which RT-qPCR was performed were confirmed (BDNF, Calb1, Dusp5, Dusp6, EGR1, NPY, RGS2). Ontological analysis indicates that several of the genes with changed expression in this study are important for behavior and learning. The importance of drug-seeking behavior and memory of previous sessions of drug-taking suggest that such genes may be important for relapse. The global gene expression analysis adds to the knowledge of heroin-induced changes and further highlights similarities between heroin and other drugs of abuse. Keywords: heroin self-administration cRNA from 6 rats that self-administered heroin was compared to cRNA from 5 rats that received yoked infusions of saline.
2009-01-29 | E-GEOD-13166 | biostudies-arrayexpress
Project description:This is a multicenter, clinical study. This study is to evaluate the sensitivity of plasma ctDNA methylation haplotypes in detecting colorectal cancer, adenoma and the specificity in healthy individuals.
| 2289244 | ecrin-mdr-crc
Project description:Determine the differential miRNA levels in plasma of heroin addicts
| PRJNA672859 | ENA