The ALDH2 rs671 Polymorphism Affects Post-Stroke Epilepsy Susceptibility and Plasma 4-HNE Levels

Yang, Heng; Song, Zhi; Yang, Guangzheng; Zhang, Bikui; Chen, Min; Wu, Tian; Guo, Ren

doi:10.1371/journal.pone.0109634

Cited by 60 publications

(60 citation statements)

References 31 publications

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“…Elevated levels of TG were associated with atherosclerosis, even in the absence of high cholesterol levels, which may be the reason why ALDH*2 allele was associated with cerebral infarction. But many other studies reported that ALDH2 protects against stroke by clearing 4-HNE (Yang et al 2014;Guo et al 2013;Lee et al 2012). Our research revealed that the ALDH2*2 allele is associated with cerebral infarction, this is consistent with the most previous studies, but further studies are needed to uncover the precise mechanism behind the regulation of ALDH2 in cerebral infarction.…”

Section: Discussionsupporting

confidence: 91%

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

Zhao

et al. 2015

Biochem Genet

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Unlike its reported role in the cardiovascular diseases, little information is available for mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the cerebrovascular function. We investigated the different effects of ALDH2 genotypes on the risk of cerebral infarction between the genders, because different genders had different smoking and/or dinking status which are also risk factors for cerebral infarction. 247 healthy Chinese Han people (controls, group 1), 287 Chinese Han male patients with cerebral infarction (group 2), and 82 Chinese Han female patients with cerebral infarction (group 3) were involved in this study. The frequencies of the ALDH2*2 allele in group 3 were significantly higher than those in other groups (with P = 0.001 and P = 0.002, respectively). The difference of ALDH2*2 allele frequency between group 1 and group 2 was not significant (P = 0.652). After adjustment for smoking and drinking status, the male patients without smoking or drinking status (group 4) had higher ALDH2*2 allele frequency than group 1, but the difference was still not significant (P = 0.139). Thus, we conclude that ALDH2*2 allele may be a significant negative risk factor for cerebral infarction in Chinese women [odds ratio (OR) = 2.207, 95% CI 1.416-3.439]. But for Chinese male patients, the negative effects of ALDH2*2 allele on cerebral infarction which might be concealed by other risk factors were not significant.

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Section: Discussionsupporting

confidence: 91%

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

Zhao

et al. 2015

Biochem Genet

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“…Other reports have implicated glutamic acid decarboxylase, glutamate transport genes, and the adenosine A1 receptor . Only 2 studies have reported genetic associations with poststroke epilepsy (PSE); 1 identified a polymorphism in a TNF receptor, CD4, and the other in mitochondrial aldehyde dehydrogenase 2 . Much more work is required to verify these findings as well as their biological relevance.…”

Section: Genetic Aspects In Patientsmentioning

confidence: 99%

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

et al. 2017

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Summary The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%‐70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification. Acquired human epilepsies with different etiologies share some features with animal models. We identify these commonalities and discuss their relevance to the development of successful epilepsy prevention or disease modification strategies. Risk factors for developing epilepsy that appear common to multiple acute injury etiologies include intracranial bleeding, disruption of the blood‐brain barrier, more severe injury, and early seizures within 1 week of injury. In diverse human epilepsies and animal models, seizures appear to propagate within a limbic or thalamocortical/corticocortical network. Common histopathologic features of epilepsy of diverse and mostly focal origin are microglial activation and astrogliosis, heterotopic neurons in the white matter, loss of neurons, and the presence of inflammatory cellular infiltrates. Astrocytes exhibit smaller K+ conductances and lose gap junction coupling in many animal models as well as in sclerotic hippocampi from temporal lobe epilepsy patients. There is increasing evidence that epilepsy can be prevented or aborted in preclinical animal models of acquired epilepsy by interfering with processes that appear common to multiple acute injury etiologies, for example, in post–status epilepticus models of focal epilepsy by transient treatment with a trkB/PLCγ1 inhibitor, isoflurane, or HMGB1 antibodies and by topical administration of adenosine, in the cortical fluid percussion injury model by focal cooling, and in the albumin posttraumatic epilepsy model by losartan. Preclinical studies further highlight the roles of mTOR1 pathways, JAK‐STAT3, IL‐1R/TLR4 signaling, and other inflammatory pathways in the genesis or modulation of epilepsy after brain injury. The wealth of commonalities, diversity of molecular targets identified preclinically, and likely multidimensional nature of epileptogenesis argue for a combinatorial strategy in prevention therapy. Going forward, the identification of impending epilepsy biomarkers to allow better patient selection, together with better alignment with multisite preclinical trials in animal models, should guide the clinical testing of new hypotheses for epileptogenesis and its prevention.

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“…In addition, the incidence of post‐stroke seizure was found to be higher in anterior circulation (11%) than lacunar (1%) strokes . Although only a few studies have discussed the role of genetics, some studies suggest that epileptogenesis in stroke survivors can be modulated by non‐overlapping polymorphisms . No significant association among STRE and ischaemic stroke subtypes (cardio‐embolic vs. atherosclerotic), sex, comorbidities (e.g.…”

Section: Epidemiologymentioning

confidence: 99%

Stroke‐related epilepsy

Feyissa

Hasan

Meschia

2018

Euro J of Neurology

119

120

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Stroke is the cause of about 10% of all epilepsy and 55% of newly diagnosed seizures among the elderly. Although recent advances in acute stroke therapy have improved longevity, there has been a consequent rise in the prevalence of stroke-related epilepsy (STRE). Many clinical studies make a distinction between early (within 7 days of onset of stroke) and late (beyond 7 days of onset of stroke) seizures based on presumed pathophysiological differences. Although early seizures are thought to be the consequence of local metabolic disturbances without altered neuronal networks, late seizures are thought to occur when the brain has acquired a predisposition for seizures. Overall, STRE has a good prognosis, being well controlled by antiepileptic drugs. However, up to 25% of cases become drug resistant. STRE can also result in increased morbidity, longer hospitalization, greater disability at discharge and greater resource utilization. Additional controlled trials are needed to explore the primary and secondary prevention of STRE as well as to provide highquality evidence on efficacy and tolerability of antiepileptic drugs to guide treatment of STRE. Robust pre-clinical and clinical prediction models of STRE are also needed to develop treatments to prevent the transformation of infarcted tissue into an epileptic focus.

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The ALDH2 rs671 Polymorphism Affects Post-Stroke Epilepsy Susceptibility and Plasma 4-HNE Levels

Cited by 60 publications

References 31 publications

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Stroke‐related epilepsy

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