Correlation analysis between MTHFR gene C677T polymorphism, serum apolipoprotein E concentration, and traumatic brain injury epilepsy
Abstract
Objective: This study investigates the correlation between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism, serum apolipoprotein E (ApoE) concentration, and the risk of epilepsy following traumatic brain injury (TBI), aiming to identify potential biomarkers for early diagnosis and intervention. Methods: A total of 60 patients with post-traumatic epilepsy (observation group) and 60 healthy controls were included. Serum ApoE concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and MTHFR C677T polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analysis included binary logistic regression to identify independent risk factors and Spearman rank correlation to evaluate relationships between variables. Results: Serum ApoE levels were significantly higher in the observation group (36.26 ± 6.16 mg/L) compared to controls (30.19 ± 5.27 mg/L, P < 0.001). The frequency of the TT genotype and C allele was also markedly elevated in the observation group (TT: 41.67% vs. 8.33%; C allele: 56.67% vs. 31.67%, both P < 0.05). Logistic regression analysis identified TT genotype (OR = 6.271, P < 0.001) and elevated ApoE levels (OR = 6.572, P < 0.001) as independent risk factors. A positive correlation between ApoE levels and the TT genotype was observed (r = 0.629, P < 0.001). Conclusion: The MTHFR C677T polymorphism and serum ApoE concentration are strongly associated with epilepsy after TBI. These findings suggest that they could serve as biomarkers for early identification of high-risk individuals, paving the way for targeted prevention and management strategies.
References
1. Agrawal A, Timothy J, Pandit L, et al. Post-traumatic epilepsy: an overview. Clinical Neurology and Neurosurgery, 2006, 108(5): 433-439.
2. Verellen R M, Cavazos J E. Post-traumatic epilepsy: an overview. Therapy, 2010, 7(5): 527.
3. Ding K, Gupta P K, Diaz-Arrastia R. Epilepsy after traumatic brain injury. Translational Research in Traumatic Brain Injury, 2016.
4. Pitkänen A, Immonen R. Epilepsy related to traumatic brain injury. Neurotherapeutics, 2014, 11(2): 286-296.
5. Lucke-Wold B P, Nguyen L, Turner R C, et al. Traumatic brain injury and epilepsy: underlying mechanisms leading to seizure. Seizure, 2015, 33: 13-23.
6. Pitkänen A, Paananen T, Kyyriäinen J, et al. Biomarkers for posttraumatic epilepsy. Epilepsy & Behavior, 2021, 121: 107080.
7. Nathoo N, Chetty R, Van Dellen J R, et al. Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E. Molecular Pathology, 2003, 56(3): 132.
8. Fordington S, Manford M. A review of seizures and epilepsy following traumatic brain injury. Journal of Neurology, 2020, 267(10): 3105-3111.
9. Curia G, Lucchi C, Vinet J, et al. Pathophysiogenesis of mesial temporal lobe epilepsy: is prevention of damage antiepileptogenic? . Current Medicinal Chemistry, 2014, 21(6): 663-688.
10. Mclntosh T K, Smith D H, Meaney D F, et al. Neuropathological sequelae of traumatic brain injury: Relationship to neurochemical and biomechanical. Laboratory Investigation, 1996, 74(2): 315.
11. Maas A I R, Menon D K, Manley G T, et al. Traumatic brain injury: progress and challenges in prevention, clinical care, and research. The Lancet Neurology, 2022, 21(11): 1004-1060.
12. Ueland P M, Hustad S, Schneede J, et al. Biological and clinical implications of the MTHFR C677T polymorphism. Trends in Pharmacological Sciences, 2001, 22(4): 195-201.
13. Kamboh M I. Apolipoprotein E polymorphism and susceptibility to Alzheimer’s disease. Human Biology, 1995, 195-215.
14. Golub V M, Reddy D S. Post-traumatic epilepsy and comorbidities: advanced models, molecular mechanisms, biomarkers, and novel therapeutic interventions. Pharmacological reviews, 2022, 74(2): 387-438.
15. Hoefer I E, Steffens S, Ala-Korpela M, et al. Novel methodologies for biomarker discovery in atherosclerosis. European Heart Journal, 2015, 36(39): 2635-2642.
16. Gudnason V, Stansbie D, Scott J, et al. C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. Atherosclerosis, 1998, 136(2): 347-354.
17. Leclerc D, Sibani S, Rozen R. Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. MTHFR Polymorphisms and Disease, 2005, 15: 1-20.
18. Yuan W H, Wang S J. Posttraumatic epilepsy after traumatic brain injury and prophylactic administration of antiepileptic drugs. Journal of the Chinese Medical Association, 2020, 83(10): 885-886.
19. Laing J, Gabbe B, Chen Z, et al. Risk factors and prognosis of early posttraumatic seizures in moderate to severe traumatic brain injury. JAMA neurology, 2022, 79(4): 334-341.
20. Cortese C, Motti C. MTHFR gene polymorphism, homocysteine and cardiovascular disease. Public Health Nutrition, 2001, 4(2b): 493-497.
21. Liew S C, Gupta E D. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. European Journal of Medical Genetics, 2015, 58(1): 1-10.
22. Samii A, Aslani S, Imani D, et al. MTHFR gene polymorphisms and susceptibility to myocardial infarction: Evidence from meta-analysis and trial sequential analysis. IJC Heart & Vasculature, 2023, 49: 101293. https://doi.org/10.1016/j.ijcha.2023.101293
23. Raghubeer S, Matsha T E. Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks. Nutrients, 2021, 13(12): 4562. https://doi.org/10.3390/nu13124562
24. Magdaleno Roman J Y, Chapa González C. Glutamate and excitotoxicity in central nervous system disorders: ionotropic glutamate receptors as a target for neuroprotection. Neuroprotection, 2024, 2: 137-150. https://doi.org/10.1002/nep3.46
25. Jain K K. Personalized Therapy of Neurological Disorders. In: Textbook of Personalized Medicine. Springer, Cham. 2020. https://doi.org/10.1007/978-3-030-62080-6_11
26. Schriml L M, Lichenstein R, Bisordi K. et al. Modeling the enigma of complex disease etiology. J Transl Med, 2023, 21: 148. https://doi.org/10.1186/s12967-023-03987-x
27. Cordaro M, Siracusa R, Fusco R, et al. Involvements of Hyperhomocysteinemia in Neurological Disorders. Metabolites, 2021, 11(1): 37. https://doi.org/10.3390/metabo11010037
28. Luzzi S, Cherubini V, Falsetti L, et al. Homocysteine, cognitive functions, and degenerative dementias: State of the art. Biomedicines, 2022, 10(11): 2741. https://doi.org/10.3390/biomedicines10112741
29. Wang K K, Munoz Pareja J C, Mondello S, et al. Blood-based traumatic brain injury biomarkers–Clinical utilities and regulatory pathways in the United States, Europe and Canada. Expert Rev Mol Diagn, 2021, 21(12): 1303-1321. https://doi.org/10.1080/14737159.2021.2005583
30. Hossain I, Marklund N, Czeiter E, et al. Blood biomarkers for traumatic brain injury: A narrative review of current evidence. Brain & Spine, 2023, 4: 102735. https://doi.org/10.1016/j.bas.2023.102735
Copyright (c) 2025 Author(s)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright on all articles published in this journal is retained by the author(s), while the author(s) grant the publisher as the original publisher to publish the article.
Articles published in this journal are licensed under a Creative Commons Attribution 4.0 International, which means they can be shared, adapted and distributed provided that the original published version is cited.
Submit a Paper
