Background/aims: Drug metabolizing enzymes may be related to drug-induced liver injury (DILI). Manganese superoxide dismutase (MnSOD), NAD(P)H:quinone oxidoreductase (NQO1), and glutathione S-transferase (GST) are important drug metabolizing enzymes. We aimed to elucidate the relationship between genetic polymorphisms of these enzymes and the susceptibility to DILI.
Methods: A total of 115 patients with DILI and 115 drug-, sex-, and age-matched controls were enrolled. Their genetic polymorphisms of MnSOD, NQO1, GSTM1, and GSTT1 were assayed.
Results: Sixty-three (54.8%) of DILI patients were incriminated to anti-tuberculosis drugs. Subjects with a mutant C allele (T/C or C/C genotype) of MnSOD had a higher risk of DILI than those with MnSOD T/T genotype, both in overall drugs studied (adjusted OR: 2.44, 95% C.I.: 1.38-4.30, P=0.002), and in sub-category of anti-tuberculosis drugs (adjusted OR: 2.47, 95% C.I.: 1.13-5.39, P=0.02). In addition, subjects carrying GSTM1 null genotype had increased risk of anti-tuberculosis DILI (adjusted OR: 2.23, 95% C.I.: 1.07-4.67, P=0.03).
Conclusions: The MnSOD mutant C allele may increase the susceptibility to DILI, and GSTM1 null genotype may be related to anti-tuberculosis drug-induced hepatotoxicity. Determination of the MnSOD and GSTM1 genotypes may help identify patients at high risk for DILI.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jhep.2007.02.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genetic determinants of COVID-19 severity and mortality: Alu 287 bp polymorphism and , , expression in hospitalized patients.
PeerJ
January 2025
Departamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Background: The angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are central human molecules in the SARS-CoV-2 virus-host interaction. Evidence indicates that may influence expression. This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA expression levels, along with the ACE1 Alu 287 bp polymorphism (rs4646994), contribute to the severity and mortality of COVID-19.
View Article and Find Full Text PDFTargeted correction of megabase-scale duplication in induced pluripotent stem cells and impacts on gene expression.
PeerJ
January 2025
Genomic Mechanisms of Ontogenesis, Institute of Cytology and Genetics, Novosibirsk, Novosibirsk, Russia.
Copy number variations of the human gene, resulting from megabase-scale microdeletions or microduplications in the 3p26.3 region, are frequently implicated in neurodevelopmental disorders such as intellectual disability and developmental delay. However, duplication of the full-length human gene presents with variable penetrance, resulting in phenotypes that range from neurodevelopmental disorders to no visible pathologies, even within the same family.
View Article and Find Full Text PDFConnections Across Open Water: A Bi-Organelle, Genomics-Scale Assessment of Atlantic-Wide Population Dynamics in a Pelagic, Endangered Apex Predator Shark ().
Evol Appl
January 2025
Save Our Seas Foundation Shark Research Center, Halmos College of Arts & Sciences Nova Southeastern University Dania Florida USA.
Large-bodied pelagic sharks are key regulators of oceanic ecosystem stability, but highly impacted by severe overfishing. One such species, the shortfin mako shark (), a globally widespread, highly migratory predator, has undergone dramatic population reductions and is now Endangered (IUCN Red List), with Atlantic Ocean mako sharks in particular assessed by fishery managers as overfished and in need of urgent, improved management attention. Genomic-scale population assessments for this apex predator species have not been previously available to inform management planning; thus, we investigated the population genetics of mako sharks across the Atlantic using a bi-organelle genomics approach.
View Article and Find Full Text PDFThe rs1800012 polymorphism is associated with osteoporosis or fracture risk: a meta-analysis of 30 studies.
Int J Burns Trauma
December 2024
Department of Orthopedics, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei, China.
Objectives: Osteoporosis is a complex disease that is influenced by several genetic markers. Many studies have examined the link between the gene rs1800012 polymorphism and osteoporosis risk. However, the findings of these studies are contradictory.
View Article and Find Full Text PDFsingle nucleotide polymorphism reduces dabigatran acylglucuronide formation in humans.
Front Pharmacol
January 2025
Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Background: Dabigatran etexilate (DABE), a prodrug of dabigatran (DAB), is a direct thrombin inhibitor used to prevent ischemic stroke and thromboembolism during atrial fibrillation. The effect of genetic polymorphisms on its metabolism, particularly , has not been extensively explored in humans. This study aimed to investigate the effects of , , and polymorphisms on the pharmacokinetics of DAB and its acylglucuronide metabolites in healthy subjects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!