Polymorphisms in the receptor for advanced glycation end products gene are associated with susceptibility to drug-resistant epilepsy

Guo, Muxing; Wang, Jiafeng; Qi, Huili; Liu, Fei; Yao, Lifen; Zhang, Shuyan; Li, Keshen

doi:10.1016/j.neulet.2016.01.043

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…In seizing mice, RAGE was upregulated, while RAGE knockout mice had reduced seizure activity [23]. The presence of G28S polymorphism in RAGE was significantly more common in patients with drug-resistant epilepsy in a study [25]. In individuals with epilepsy, increased blood sugar levels have been reported, which may be associated with AGE and poor seizure control in childhood epilepsy.…”

Section: Discussionmentioning

confidence: 91%

“…Receptor for AGE (RAGE) is found in different cells. When RAGE binds to AGE, nuclear factor kappa B (NFkB) is activated and releases inflammatory mediators, which contributes to inflammation, intracellular damage and apoptosis [23][24][25]. In brain biopsy samples of individuals with temporal lobe epilepsy, RAGE was upregulated in astrocytes, neurons, and microvessels and was reported to contribute to seizures [23].…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test

Silver

Bahl

Cordeiro

et al. 2021

Genes

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Introduction: Childhood epilepsy is one of the most common neurological problems. The transferrin isoelectric focusing (TIEF) test is a screening test for congenital disorders of glycosylation (CDG). We identified abnormal TIEF test in children with epilepsy in our epilepsy genetics clinic. To determine if an abnormal TIEF test is associated with anti-epileptic medications or abnormal liver functions, we performed a retrospective cohort study. Methods: This study was performed between January 2012 and March 2020. Electronic patient charts were reviewed. Standard non-parametric statistical tests were applied using R statistical software. Fischer’s exact test was used for comparisons. Results: There were 206 patients. The TIEF test was abnormal in 11% (23 out of 206) of the patients. Nine patients were diagnosed with CDG: PMM2-CDG (n = 5), ALG3-CDG (n = 1), ALG11-CDG (n = 2), SLC35A2-CDG (n = 1). We report 51 different genetic diseases in 84 patients. Two groups, (1) abnormal TIEF test; (2) normal TIEF test, showed statistically significant differences for abnormal liver functions and for valproic acid treatment. Conclusion: The TIEF test guided CDG diagnosis in 2.9% of the patients. Due to the high prevalence of CDG (4.4%) in childhood epilepsy, the TIEF test might be included into the diagnostic investigations to allow earlier and cost-effective diagnosis.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test

Silver

Bahl

Cordeiro

et al. 2021

Genes

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“…Compared with its ligand HMGB1, RAGE activity likely plays a pivotal role in the transduction of inflammatory signals. Recently, a dominant inheritance model of the G82S locus in RAGE was observed to be protective against drug-resistant epilepsy (Guo et al, 2016 ), providing genetic support for the involvement of RAGE in epileptic seizures.…”

Section: Downstream Rage In Epilepsymentioning

confidence: 99%

Conflicting Effects of Methylglyoxal and Potential Significance of miRNAs for Seizure Treatment

Tao

Zhou

Zhao

et al. 2018

Front. Mol. Neurosci.

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According to an update from the World Health Organization, approximately 50 million people worldwide suffer from epilepsy, and nearly one-third of these individuals are resistant to the currently available antiepileptic drugs, which has resulted in an insistent pursuit of novel strategies for seizure treatment. Recently, methylglyoxal (MG) was demonstrated to serve as a partial agonist of the gamma-aminobutyric acid type A (GABAA) receptor and to play an inhibitory role in epileptic activities. However, MG is also a substrate in the generation of advanced glycation end products (AGEs) that function by activating the receptor of AGEs (RAGE). The AGE/RAGE axis is responsible for the transduction of inflammatory cascades and appears to be an adverse pathway in epilepsy. This study systematically reviewed the significance of GABAergic MG, glyoxalase I (GLO1; responsible for enzymatic catalysis of MG cleavage) and downstream RAGE signaling in epilepsy. This work also discussed the potential of miRNAs that target multiple mRNAs and introduced a preliminary scheme for screening and validating miRNA candidates with the goal of reconciling the conflicting effects of MG for the future development of seizure treatments.

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“…The relevant functional polymorphisms of RAGE were analyzed in a case‐control study in an Asian population. A total of 274 healthy adults and 280 adult patients with epilepsy (140 patients controlled epilepsy and 140 with DRE) were evaluated 107 . In this study, the results were analyzed are included −429 C/T (rs1800625), −374 T/A (rs1800624), and G82S (rs2070600).…”

Section: Introductionmentioning

confidence: 99%

“…In this study, the results were analyzed are included −429 C/T (rs1800625), −374 T/A (rs1800624), and G82S (rs2070600). They found that the homozygous and heterozygous (T/T + C/T) T allele of the genetic variant G82S (rs2070600) exhibited significant differences between healthy individuals and drug‐resistant epileptic patients, identifying it as a risk factor for DRE 107 . The structural change of glycine to serine may display higher affinity for ligands, resulting in increased inflammatory mediators after RAGE activation 108 .…”

Section: Introductionmentioning

confidence: 99%

Factors not considered in the study of drug‐resistant epilepsy: Drug‐resistant epilepsy: Assessment of neuroinflammation

2022

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More than one-third of people with epilepsy develop drug-resistant epilepsy (DRE). Different hypotheses have been proposed to explain the origin of DRE.Accumulating evidence suggests the contribution of neuroinflammation, modifications in the integrity of the blood-brain barrier (BBB), and altered immune responses in the pathophysiology of DRE. The inflammatory response is mainly due to the increase of cytokines and related molecules; these molecules have neuromodulatory effects that contribute to hyperexcitability in neural networks that cause seizure generation. Some patients with DRE display the presence of autoantibodies in the serum and mainly cerebrospinal fluid. These patients are refractory to the different treatments with standard antiseizure medications (ASMs), and they could be responding well to immunomodulatory therapies. This observation emphasizes that the etiopathogenesis of DRE is involved with immunology responses and associated long-term events and chronic inflammation processes. Furthermore, multiple studies have shown that functional polymorphisms as risk factors are involved in inflammation processes.Several relevant polymorphisms could be considered risk factors involved in inflammation-related DRE such as receptor for advanced glycation end products (RAGE) and interleukin 1β (IL-1β). All these evidences sustained the hypothesis that the chronic inflammation process is associated with the DRE. However, the effect of the chronic inflammation process should be investigated in further clinical studies to promote the development of novel therapeutics useful in treatment of DRE.

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Polymorphisms in the receptor for advanced glycation end products gene are associated with susceptibility to drug-resistant epilepsy

Cited by 9 publications

References 33 publications

Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test

Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test

Conflicting Effects of Methylglyoxal and Potential Significance of miRNAs for Seizure Treatment

Factors not considered in the study of drug‐resistant epilepsy: Drug‐resistant epilepsy: Assessment of neuroinflammation

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