ArticleStroke2007
Promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene: a novel risk factor for arterial ischemic stroke among young adults and children.
Article in Stroke, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 141 citations in OpenAlex.
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- From Serum to Genome: γ-Glutamyltransferase Gene Family Variants Shape Ischemic Stroke Risk via Sex-Specific Gene-Environment Interactions.Life (Basel, Switzerland) · 2026Article
- Integrative proteomic and metabolomic analysis reveals the mechanisms underlying ischemic stroke induced by vitamin B12 deficiency.European journal of nutrition · 2025Article
- Study on the molecular aspect of cardioprotective effects of selenium: a mini-review.Journal of basic and clinical physiology and pharmacology · 2025Review
- Cardiovascular Manifestations of Patients with Long COVID.Diagnostics (Basel, Switzerland) · 2025Article
- In Silico Prediction of Functional SNPs Interrupting Antioxidant Defense Genes in Relation to COVID-19 Progression.Biochemical genetics · 2025Article
- Circulating Glutathione Peroxidase-3 in Elderly-Association with Renal Function, Cardiovascular Mortality, and Impact of Selenium and Coenzyme QAntioxidants (Basel, Switzerland) · 2024Article
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- Evaluation of Glutathione in Spike Protein of SARS-CoV-2 Induced Immunothrombosis and Cytokine Dysregulation.Antioxidants (Basel, Switzerland) · 2024Article
- Targeting Cysteine Oxidation in Thrombotic Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Oxidative stress as a bridge between age and stroke: A narrative review.Journal of intensive medicine · 2023Review
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- Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID.International journal of molecular sciences · 2023Article
- The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review.Frontiers in bioscience (Landmark edition) · 2023Review
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- Serum Metabolomics and Proteomics to Study the Antihypertensive Effect of Protein Extracts fromNutrients · 2022Article
- Redox Mechanisms of Platelet Activation in Aging.Antioxidants (Basel, Switzerland) · 2022Review
- The Impact of Genetic Polymorphisms in Glutamate-Cysteine Ligase, a Key Enzyme of Glutathione Biosynthesis, on Ischemic Stroke Risk and Brain Infarct Size.Life (Basel, Switzerland) · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
background and purposePlasma glutathione peroxidase (GPx-3)-deficiency increases extracellular oxidant stress, decreases bioavailable nitric oxide, and promotes platelet activation. The aim of this study is to identify polymorphisms in the GPx-3 gene, examine their relationship to arterial ischemic stroke (AIS) in a large series of children and young adults, and determine their functional molecular consequences.
methodsWe studied the GPx-3 gene promoter from 123 young adults with idiopathic AIS and 123 age- and gender-matched controls by single-stranded conformational polymorphism and sequencing analysis. A second, independent population with childhood stroke was used for a replication study. We identified 8 novel, strongly linked polymorphisms in the GPx-3 gene promoter that formed 2 main haplotypes (H1 and H2). The transcriptional activity of the 2 most prevalent haplotypes was studied with luciferase reporter gene constructs.
resultsThe H2 haplotype was over-represented in both patient populations and associated with an independent increase in the risk of AIS in young adults (odds ratio=2.07, 95% CI=1.03 to 4.47; P=0.034) and children (odds ratio=2.13, 95% CI=1.23 to 4.90; P=0.027). In adults simultaneously exposed to vascular risk factors, the risk of AIS approximately doubled (odds ratio=5.18, 95% CI=1.82 to 15.03; P<0.001). Transcriptional activity of the H2 haplotype was lower than that of the H1 haplotype, especially after upregulation by hypoxia (normalized relative luminescence: 3.54+/-0.32 versus 2.47+/-0.26; P=0.0083).
conclusionsThese findings indicate that a novel GPx-3 promoter haplotype is an independent risk factor for AIS in children and young adults. This haplotype reduces the gene's transcriptional activity, thereby compromising gene expression and plasma antioxidant and antithrombotic activities.
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