Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy

Zhu, Shaofang; Ni, Guanzhong; Sui, Lisen; Zhao, Yiran; Zhang, Xiaoxu; Dai, Qilin; Chen, Aohan; Lin, Wanrong; Li, Yinchao; Huang, Min; Zhou, Liemin

doi:10.3389/fneur.2021.683275

Cited by 10 publications

(16 citation statements)

References 48 publications

(62 reference statements)

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“…The authors did not demonstrate genotype distributions. However, in the study, the MTHFR TT genotype was observed to increase patients' susceptibility to the effect of oxcarbazepine in disrupting homocysteine homeostasis [33].…”

Section: Discussionmentioning

confidence: 70%

“…Vurucu et al [32] demonstrated that 677C>T polymorphism of the MTHFR gene had no impact on elevated levels of homocysteine in epileptic children receiving carbamazepine or valproic acid. In addition, a recent study by Zhu et al [33] analyzed MTHFR polymorphism in epileptic patients and controls aged 15-55 years old but in reference to its impact on homocysteine levels. The authors did not demonstrate genotype distributions.…”

Section: Discussionmentioning

confidence: 99%

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Is There a Relation between 677C>T Polymorphism in the MTHFR Gene and the Susceptibility to Epilepsy in Young Patients? A Meta-Analysis

Sarecka-Hujar

2021

Brain Sciences

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Background: Numerous data show a role for genetic polymorphisms in the development of epilepsy. Previously, the TT genotype of the MTHFR 677C>T polymorphism was found to be associated with a decreased leucocyte DNA methylation status. Polymorphisms in the MTHFR gene could modify the pharmacodynamics of many drugs. This meta-analysis aimed to assess the relationship between MTHFR 677C>T polymorphism and susceptibility to epilepsy in young patients. Methods: Available databases (PubMed, Embase, Google Scholar, SciELO, and Medline) were searched using specific keywords. Eight studies, published between 1999 and 2019, with 1678 young patients with epilepsy and 1784 controls, met the inclusion criteria. Apart from the total groups, additional analyses in age subgroups (i.e., young adults and children) were conducted. Statistical analyses were conducted using the RevMan 5.4 and MedCalc software. The pooled odds ratio (OR) was estimated with a random- or fixed-effects model depending on the heterogeneity. Analyses were performed for five genetic models, i.e., dominant (CT + TT vs. CC), recessive (TT vs. CC + CT), additive (TT vs. CC), heterozygous (CT vs. CC), and allelic (T vs. C). The publication bias was assessed with the use of Egger’s and Begg’s tests. Results: Both the MTHFR TT genotype (in the additive model) and the T allele (in the allelic model) significantly increased the risk of epilepsy when the total groups were compared (OR = 1.44, p = 0.002, and OR = 1.183, p = 0.001, respectively). The sensitivity analysis for these models indicated the stability of the results. Similarly, significant results were obtained among young adults for all the genetic models (dominant model: OR = 1.28, p = 0.002; recessive model: OR = 1.48, p = 0.003; additive model: OR = 1.63, p < 0.001; heterozygous model: OR = 1.21, p = 0.028; and allelic model: OR = 1.256, p < 0.001). Those results were also stable and reliable. In the group of children, no relation between 677C>T polymorphism and epilepsy was observed; however, the analysis was based only on three studies, and one study also comprised young adults. No publication bias was demonstrated. Conclusions: The meta-analysis revealed that the carrier state for the T allele as well as the TT genotype of the MTHFR 677C>T polymorphism increases the risk of epilepsy in young adults but not in children.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Is There a Relation between 677C>T Polymorphism in the MTHFR Gene and the Susceptibility to Epilepsy in Young Patients? A Meta-Analysis

Sarecka-Hujar

2021

Brain Sciences

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“…Independent risk factors for elevated Hcy levels in patients with epilepsy were found to influence the Hcy homeostasis 5 . Furthermore, it has been documented that epilepsy and related disorders may occur as a result of gene polymorphism in 5,10methylenetetrahydrofolate reductase (MTHFR), along with the deficiency of vitamin B-12 (methylcobalamin), folic acid, and vitamin B6 (pyridoxal phosphate) 5 .…”

Section: Introductionmentioning

confidence: 96%

“…Some of the major causes are a head injury, brain infections like meningitis or encephalitis, brain tumors, birth defects, stroke, and even altered levels of blood components like sodium or blood sugar. Homocysteine (Hcy), a non-proteinogenic α-amino acid that is produced during methionine metabolism, is one blood component that may elevate in concentration mainly due to the deficiency of folic acid and/or vitamin B-12 leading to various risks [3][4][5] . Independent risk factors for elevated Hcy levels in patients with epilepsy were found to influence the Hcy homeostasis 5 .…”

Section: Introductionmentioning

confidence: 99%

“…Homocysteine (Hcy), a non-proteinogenic α-amino acid that is produced during methionine metabolism, is one blood component that may elevate in concentration mainly due to the deficiency of folic acid and/or vitamin B-12 leading to various risks [3][4][5] . Independent risk factors for elevated Hcy levels in patients with epilepsy were found to influence the Hcy homeostasis 5 . Furthermore, it has been documented that epilepsy and related disorders may occur as a result of gene polymorphism in 5,10methylenetetrahydrofolate reductase (MTHFR), along with the deficiency of vitamin B-12 (methylcobalamin), folic acid, and vitamin B6 (pyridoxal phosphate) 5 .…”

Section: Introductionmentioning

confidence: 99%

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Age Related Homocysteine Serum Levels Elevate in Men with Epilepsy

Hussain¹,

Ahmed²,

Serafi³

et al. 2022

ashkmdc

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Objective: The purpose of the present study was to determine the correlation of age with serum homocysteine (Hcy) levels in male nonobese epilepsy (Ep) patients and nonobese male control (C) subjects. Methods: This case-control study was conducted in non-obese male epilepsy patients (Ep; n: 44; age: 26-40 years) having predominant grand mal (generalized tonic-clonic) seizures, and in control subjects (C; n: 42; age: 26-40 years). The Ep and C subjects were further subdivided into age-based subgroups: 26-30, 31-35, 36-40 years. Determination of serum Hcy was carried out by enzyme linked immunosorbent assay (ELISA). SPSS software version 24 was used for the purpose of data entry/ statistical analysis. Results: The mean± SD values for serum Hcy (?mol/L) in male Ep (n:44) and male C subjects (n:42) were 12.34±3.34 and 9.16±3.38 respectively, that showed highly significant increase in the level of Hcy (p< 0.001) in Ep compared to C subjects. Serum Hcy levels showed significant increased serum levels of Hcy, and positive linear correlation in all age groups (26-30, 31-35, 36-40, 26-40) in Ep subjects compared to control subjects. However, significantly elevated serum Hcy and lesser association (though significant) of Hcy with age in Ep group as compared to C subjects was found in the present report. Conclusion: Present study provides evidence of the significant impact of age on serum homocysteine levels in nonobese epilepsy patients. However, it is essentially required to carry out well controlled studies comprising wider age range data, and large number of samples in each age subgroup to have better idea about the potential impact of Hcy in epilepsy, and to investigate the comparative effects of AEDs and dosages of AEDs on serum levels of Hcy and vice versa.

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Susceptibility to preoperative seizures in glioma patients with elevated homocysteine levels

Chi

Guo

et al. 2023

Epilepsia Open

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ObjectiveSeizures are a common clinical presentation in patients with glioma and substantially impact patients' quality of life. Hyperhomocysteinemia is defined as abnormally high serum levels of homocysteine (Hcy) and is reportedly linked to susceptibility to various nervous system diseases. However, it remains unclear whether and how hyperhomocysteinemia and its associated genetic polymorphisms promote seizures in glioma patients.MethodsWe retrospectively reviewed all medical data from 127 patients with malignant gliomas, who underwent initial tumor resection by our team between July 2019 and June 2021 and had preoperative measurements of serum Hcy levels. According to whether they had at least one seizure before surgery, they were divided into the seizure and nonseizure groups. We also detected polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and measured intratumoral Hcy levels in these patients.ResultsHyperhomocysteinemia was a susceptibility factor for preoperative seizures in glioma patients according to both univariate analyses (P < 0.001) and multivariate logistic regression analyses (OR 1.239, 95% CI 1.062–1.445, P = 0.007). Patients with the MTHFR C677T variant exhibited elevated serum Hcy levels (P = 0.027) and an increased prevalence of preoperative seizures (P = 0.019). Intratumoral Hcy levels were positively correlated with serum Hcy levels (R = 0.231, P = 0.046) and were elevated in patients with hyperhomocysteinemia (P = 0.031), the MTHFR C677T variant (P = 0.002) and preoperative seizures (P = 0.003). High intratumoral Hcy levels, rather than hyperhomocysteinemia or the MTHFR C677T variant, emerged as an independent risk factor for preoperative seizures (OR 1.303, 95% CI 1.015–1.673, P = 0.038). Furthermore, the effects of hyperhomocysteinemia on epileptic susceptibility were reduced to nonsignificance when intratumoral Hcy was controlled to the same level between groups.SignificanceGlioma patients with hyperhomocysteinemia and the MTHFR C677T variant were susceptible to preoperative seizures, suggesting their potential as biomarkers for the management of seizures in glioma patients. The elevation of intratumoral Hcy is a possible mechanism underlying this susceptibility.

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Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy

Cited by 10 publications

References 48 publications

Is There a Relation between 677C>T Polymorphism in the MTHFR Gene and the Susceptibility to Epilepsy in Young Patients? A Meta-Analysis

Is There a Relation between 677C>T Polymorphism in the MTHFR Gene and the Susceptibility to Epilepsy in Young Patients? A Meta-Analysis

Age Related Homocysteine Serum Levels Elevate in Men with Epilepsy

Susceptibility to preoperative seizures in glioma patients with elevated homocysteine levels

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