Related Experiment Video

Updated: Mar 6, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

5.5K

Genome-Wide Association Studies for Idiosyncratic Drug-Induced Hepatotoxicity: Looking Back-Looking Forward to

Zelalem Petros1, Eyasu Makonnen1, Eleni Aklillu2

  • 11 Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University , Addis Ababa, Ethiopia .

Omics : a Journal of Integrative Biology
|March 3, 2017
PubMed

Insights

Genome-wide association studies reveal genetic variants, particularly in the human leukocyte antigen region, linked to drug-induced liver injury. Understanding these genetic factors is crucial for personalized medicine and safer drug development.

Area of Science:

  • Pharmacogenomics
  • Immunology
  • Drug Development

Background:

  • Idiosyncratic drug-induced hepatotoxicity presents a significant hurdle in drug discovery and personalized medicine.
  • Hereditary factors are implicated in the variability of drug toxicity responses.

Purpose of the Study:

  • To review insights and challenges from genome-wide association studies (GWASs) for idiosyncratic drug-induced hepatotoxicity.
  • To identify genetic risk variants associated with drug-induced liver injury.

Main Methods:

  • Systematic search of PubMed for published genome-wide and replication studies on drug-induced hepatotoxicity.
  • Analysis of genetic polymorphisms identified through GWASs and subsequent validation.

Main Results:

  • Confirmed genetic risk variants primarily involve human leukocyte antigen (HLA) region polymorphisms (e.g., HLA-DQB1*06:02, HLA-B*57:01, HLA-DRB1*15:01, HLA-DRB1*07:01).
  • Polymorphisms in ST6GAL1 and FAM65B were associated with specific drug-induced hepatotoxicity cases.
  • GWAS findings highlight the immune system's role in drug-induced liver injury.

Conclusions:

  • Genetic variants, especially HLA polymorphisms, are key determinants of idiosyncratic drug-induced hepatotoxicity.
  • Future research requires integrated approaches, including GWASs, candidate gene studies, and environmental factor analysis (environtome).
  • Addressing challenges in genetic discovery is vital for advancing personalized medicine and mitigating drug toxicity.
Keywords:
GWASdisruptive innovationdrug discovery and developmentdrug-induced hepatotoxicitydrug-induced liver injurygenome-wide studytranslational research

More Related Videos

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms11:36

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms

Published on: May 29, 2020

3.5K
Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization08:27

Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization

Published on: July 27, 2021

4.9K

Related Concept Videos

Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
75
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
76
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
76
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
74
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
66
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
16.2K