Association of insulin receptor H1085H C&gt;T, insulin receptor substrate 1 G972R and insulin receptor substrate 2 1057G/A polymorphisms with refractory temporal lobe epilepsy in Han Chinese

Che, Fengyuan; Fu, Qin; Li, Xuesong; Gao, Naiyong; Qi, Faying; Sun, Zhanfang; Du, Yifeng; Li, Ming

doi:10.1016/j.seizure.2014.09.014

Cited by 8 publications

(10 citation statements)

References 12 publications

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“…Some genes fall into multiple categories, e.g. IRS2 is associated not only with diabetes and receptor mediated signal transduction for specific extracellular cytokines, but also with epilepsy ( 70 ), aspects of schizophrenia ( 43 ), Alzheimer's disease ( 71 – 73 ), retinal degeneration ( 74 ), hippocampal synaptic plasticity ( 75 ), long term potentiation of hippocampal synaptic transmission ( 76 ), ataxia ( 77 ), cardiac failure ( 78 ), kidney development ( 79 ), renal disease ( 80 ), breast cancer ( 81 , 82 ), rhabdomyosarcoma ( 83 ) and, in conjunction with JAK2 3N-hCR , hematopoesis ( 84 , 85 ). A limited study of an N-hCR length polymorphism in IRS2 shows no association with diabetes ( 86 ).…”

Section: Foundation Of the Hypothesismentioning

confidence: 99%

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

Banerji¹

2015

International Journal of Molecular Medicine

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The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.

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Section: Foundation Of the Hypothesismentioning

confidence: 99%

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

Banerji¹

2015

International Journal of Molecular Medicine

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“…Evident IR occurs in patients with chronic epilepsy [69,70], while in patients with type 1 diabetes mellitus who lack insulin, the risk of epilepsy is 3-fold that in normal controls [71]. And the H1085H C [ T polymorphism of the insulin receptor gene is associated with drug resistance in refractory epilepsy patients [72]. Insulin recruits GABA receptors to the postsynaptic membrane and dendritic membrane, regulating the electrophysiological activity of neurons via GABA receptor-dependent and independent mechanisms [73,74].…”

Section: The Role and Mechanism Of Zag In Cns Diseasesmentioning

confidence: 99%

Expression and Function of Zinc-α2-Glycoprotein

et al. 2019

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, encoded by the AZGP1 gene, is a major histocompatibility complex I molecule and a lipid-mobilizing factor. ZAG has been demonstrated to promote lipid metabolism and glucose utilization, and to regulate insulin sensitivity. Apart from adipose tissue, skeletal muscle, liver, and kidney, ZAG also occurs in brain tissue, but its distribution in brain is debatable. Only a few studies have investigated ZAG in the brain. It has been found in the brains of patients with Krabbe disease and epilepsy, and in the cerebrospinal fluid of patients with Alzheimer disease, frontotemporal lobe dementia, and amyotrophic lateral sclerosis. Both ZAG protein and AZGP1 mRNA are decreased in epilepsy patients and animal models, while overexpression of ZAG suppresses seizure and epileptic discharges in animal models of epilepsy, but knowledge of the specific mechanism of ZAG in epilepsy is limited. In this review, we summarize the known roles and molecular mechanisms of ZAG in lipid metabolism and glucose metabolism, and in the regulation of insulin sensitivity, and discuss the possible mechanisms by which it suppresses epilepsy.

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“…Furthermore, several studies have also reported associations of IRS1 polymorphisms with cancer, diabetes, glucose levels and obesity (40)(41)(42)(43)(44). Furthermore, insulin/insulin receptor signaling and the insulin-like growth factor (iGF) pathway may have different functions in the central nervous system in brain development, blood glucose regulation, dendritic growth and neuronal apoptosis (37,(45)(46)(47)(48). However, che et al (47) was unable to identify any association between the IRS1 gene and epilepsy in a chinese sample but suggested that the genes associated with the insulin signaling pathway may affect the therapeutic response of temporal lobe epilepsy.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, insulin/insulin receptor signaling and the insulin-like growth factor (iGF) pathway may have different functions in the central nervous system in brain development, blood glucose regulation, dendritic growth and neuronal apoptosis (37,(45)(46)(47)(48). However, che et al (47) was unable to identify any association between the IRS1 gene and epilepsy in a chinese sample but suggested that the genes associated with the insulin signaling pathway may affect the therapeutic response of temporal lobe epilepsy. Previous epidemiologic studies have demonstrated that ScZ and other mental illnesses may increase the risk of developing type 2 diabetes and other metabolic disorders (49,50).…”

Section: Discussionmentioning

confidence: 99%

Pyrosequencing analysis of IRS1 methylation levels in schizophrenia with tardive dyskinesia

Wang

Zhang

et al. 2020

Mol Med Report

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Tardive dyskinesia (Td) is a serious side effect of certain antipsychotic medications that are used to treat schizophrenia (ScZ) and other mental illnesses. The methylation status of the insulin receptor substrate 1 (IRS1) gene is reportedly associated with ScZ; however, no study, to the best of the authors' knowledge, has focused on the quantitative dna methylation levels of the IRS1 gene using pyrosequencing in ScZ with or without Td. The present study aimed to quantify dna methylation levels of 4 cpG sites in the IRS1 gene using a chinese sample including ScZ patients with Td and without Td (nTd) and healthy controls (Hcs). The general linear model (GlM) was used to detect dna methylation levels among the 3 proposed groups (Td vs. nTd vs. Hc). Mean dna methylation levels of 4 cpG sites demonstrated normal distribution. Pearson's correlation analysis did not reveal any significant correlations between the DNA methylation levels of the 4 cpG sites and the severity of ScZ. GlM revealed significant differences between the 3 groups for CpG site 1 and the average of the 4 cpG sites (P=0.0001 and P=0.0126, respectively). Furthermore, the Td, nTd and Td + nTd groups demonstrated lower methylation levels in cpG site 1 (P=0.0003, P<0.0001 and P<0.0001, respectively) and the average of 4 cpG sites (P=0.0176, P=0.0063 and P=0.003, respectively) compared with the Hc group. The results revealed that both nTd and Td patients had significantly decreased dna methylation levels compared with healthy controls, which indicated a significant association between the dna methylation levels of the IRS1 gene with ScZ and Td.

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Association of insulin receptor H1085H C>T, insulin receptor substrate 1 G972R and insulin receptor substrate 2 1057G/A polymorphisms with refractory temporal lobe epilepsy in Han Chinese

Abstract: These results suggest that a genetic variation in the insulin signaling pathway genes may affect the therapeutic response of TLE.

Cited by 8 publications

References 12 publications

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis)

Expression and Function of Zinc-α2-Glycoprotein

Pyrosequencing analysis of IRS1 methylation levels in schizophrenia with tardive dyskinesia

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