ArticleEpilepsia2015
Genetic variation in the adenosine regulatory cycle is associated with posttraumatic epilepsy development.
Article in Epilepsia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group.Brain imaging and behavior · 2021Pooled it
- Article
- CD73 polymorphisms are associated with schizophrenia.Purinergic signalling · 2025Article
- Adenosine Kinase: An Epigenetic Modulator and Drug Target.Journal of inherited metabolic disease · 2025Review
- Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.Molecular neurobiology · 2025Article
- Article
- Clinico-genetic Analysis of Adenosine Signaling Pathway in Drug-Resistant Epilepsy.Annals of Indian Academy of Neurology · 2025Article
- Neuroglia and brain energy metabolism.Handbook of clinical neurology · 2025Review
- New epilepsy therapies in development.Nature reviews. Drug discovery · 2024Review
- Hospital-acquired infections as a risk factor for post-traumatic epilepsy: A registry-based cohort study.Epilepsia open · 2024Article
- Targeting the adenosine AChinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- P2Y12 receptor gene polymorphisms are associated with epilepsy.Purinergic signalling · 2023Article
- Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy.Frontiers in pharmacology · 2023Article
- Astrocytes in the initiation and progression of epilepsy.Nature reviews. Neurology · 2022Review
- Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.Pharmacological reviews · 2022Review
- Genetic variations of adenosine kinase as predictable biomarkers of efficacy of vagus nerve stimulation in patients with pharmacoresistant epilepsy.Journal of neurosurgery · 2022Article
- ATP and adenosine-Two players in the control of seizures and epilepsy development.Progress in neurobiology · 2021Review
- Treelet transform analysis to identify clusters of systemic inflammatory variance in a population with moderate-to-severe traumatic brain injury.Brain, behavior, and immunity · 2021Article
- Adenosine kinase: A key regulator of purinergic physiology.Biochemical pharmacology · 2021Review
- Genetic Variation and Impact on Outcome in Traumatic Brain Injury: an Overview of Recent Discoveries.Current neurology and neuroscience reports · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveDetermine if genetic variation in enzymes/transporters influencing extracellular adenosine homeostasis, including adenosine kinase (ADK), [ecto-5'-nucleotidase (NT5E), cluster of differentiation 73 (CD73)], and equilibrative nucleoside transporter type-1 (ENT-1), is significantly associated with epileptogenesis and posttraumatic epilepsy (PTE) risk, as indicated by time to first seizure analyses.
methodsNine ADK, three CD73, and two ENT-1 tagging single nucleotide polymorphisms (SNPs) were genotyped in 162 white adults with moderate/severe traumatic brain injury (TBI) and no history of premorbid seizures. Kaplan-Meier models were used to screen for genetic differences in time to first seizure occurring >1 week post-TBI. SNPs remaining significant after correction for multiple comparisons were examined using Cox proportional hazards analyses, adjusting for subdural hematoma, injury severity score, and isolated TBI status. SNPs significant in multivariate models were then entered simultaneously into an adjusted Cox model.
resultsComparing Kaplan-Meier curves, rs11001109 (ADK) rare allele homozygosity and rs9444348 (NT5E) heterozygosity were significantly associated with shorter time to first seizure and an increased seizure rate 3 years post-TBI. Multivariate Cox proportional hazard models showed that these genotypes remained significantly associated with increased PTE hazard up to 3 years post-TBI after controlling for variables of interest (rs11001109: hazard ratio (HR) 4.47, 95% confidence interval (CI) 1.27-15.77, p = 0.020; rs9444348: HR 2.95, 95% CI 1.19-7.31, p = 0.019) . SIGNIFICANCE: Genetic variation in ADK and NT5E may help explain variability in time to first seizure and PTE risk, independent of previously identified risk factors, after TBI. Once validated, identifying genetic variation in adenosine regulatory pathways relating to epileptogenesis and PTE may facilitate exploration of therapeutic targets and pharmacotherapy development.
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