Association Of the Methylene Tetrahydrofolate Reductase (MTHFR) Gene Polymorphism with Susceptibility to Recurrence of Cardiovascular Outcomes Among Ischemic Stroke- A Randomized Controlled Trial
DOI:
https://doi.org/10.55489/njcm.131020222420Keywords:
Gene polymorphism, Ischemic stroke, homocysteine, recurrence, cardiovascular disordersAbstract
Background: Hyperhomocystenemia and genetic variants are factors for causing young age stroke globally. This study aims to identify homocysteine related-MTHFR gene polymorphism that associated with recur-rent cardiovascular outcomes.
Methodology: A randomized controlled trial conducted upon 90 hyperhomocysteinemic ischemic stroke patients were taken from the neurology wards of a tertiary care hospital were randomly selected into vita-min B therapy group and control groups (n=45 in each group). Baseline subject details were collected ve-nous blood sample for MTHFR genetic testing via PCR-RFLP technique along with blood homocysteine lev-els, vitamin B12, folic acid levels.
Results: The results showed that the frequency of CT genotype polymorphism was 15.5% vs 13.3% for the MTHFR C677T gene without any significant difference between vitamin group and control group respective-ly (p-value >0.05). The reduction in mean homocysteine up to -6.77±4.50 versus -2.08±0.71 µmol/L in the vitamin group as compared to control group respectively, p value 0.001.
Conclusion: Considerable amount of MTHFR gene polymorphism found among hyperhomocysteinemic is-chemic stroke of sub-Himalayan region. Nutritional deficiencies including vitamin B 12 & folic acid, and some hidden reasons found, which could lead to the primary cause of hyperhomocysteinemia. Vitamin B therapy is an effective for reducing homocysteine.
References
Pandian, Jeyaraj D, and Paulin S. Stroke Epidemiology and Stroke Care Services in India." Journal of Stroke 2013; 15 (3): 128. https://doi.org/10.5853/jos.2013.15.3.128. Doi: https://doi.org/10.5853/jos.2013.15.3.128 PMid:24396806 PMCid:PMC3859004
Hashimoto, Takao, Yoshihiko S., and Hiroshi H Homocysteine Metabolism. 2007; 127 (10): 1579-92. Doi: https://doi.org/10.1248/yakushi.127.1579 PMid:17917419
Bhargava S, Ali A, Bhargava EK, Manocha A, Kankra M, Das S, et al. Lowering homocysteine and modifying nutritional status with fo-lic acid and vitamin B12in Indian patients of vascular disease. J Clin Biochem Nutr.May 2012; 50 (3):222-6. Doi: https://doi.org/10.3164/jcbn.11-72 PMid:22573925 PMCid:PMC3334376
Biswas, Arijit, R. R., Arvind M., Mohammad S. A., Birendra K. Y., Murali M., Vivekanandhan S.et al. Homocysteine Levels, Polymor-phisms and the Risk of Ischemic Stroke in Young Asian Indians. Journal of Stroke and Cerebrovascular Diseases 2009; 18 (2): 103-10. Doi: https://doi.org/10.1016/j.jstrokecerebrovasdis.2008.09.014 PMid:19251185
Fezeu L, Ducros V, Guéant J, Guilland J, Andreeva V, Hercberg S et al. MTHFR 677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 randomized controlled 101 trial. 2018; PLOS ONE 13 (5):e0193352. Doi: https://doi.org/10.1371/journal.pone.0193352 PMid:29813097 PMCid:PMC5973566
Cotlarciuc I, Malik R, Holliday E, Ahmadi K, Paré G, Psaty B et al. Effect of Genetic Variants Associated With Plasma Homocysteine Levels on Stroke Risk. Stroke 2014; 45 (7):1920-1924. Doi: https://doi.org/10.1161/STROKEAHA.114.005208 PMid:24846872 PMCid:PMC4083192
Huo, Yong, Jianping Li, Xianhui Q., Yining H., Xiaobin W., Rebecca F. Gottesman, Genfu T., et al. Efficacy of Folic Acid Therapy in Prima-ry Prevention of Stroke among Adults with Hypertension in China: The CSPPT Randomized Clinical Trial. JAMA - Journal of the American Medical Association 2015; 313 (13): 1325-35. Doi: https://doi.org/10.1001/jama.2015.2274 PMid:25771069
Alluri, R. V., V. Mohan, S. Komandur, K. C., J. R. C., and Qurratulain H. MTHFR C677T Gene Mutation as a Risk Factor for Arterial Stroke: A Hospital Based Study. European Journal of Neurology 2005; 12 (1). Doi: https://doi.org/10.1111/j.1468-1331.2004.00938.x PMid:15613145
Lewis S, Ebrahim S, Smith G. Meta-analysis of MTHFR 677C→ T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ 2005; 331(7524):1053. Doi: https://doi.org/10.1136/bmj.38611.658947.55 PMid:16216822 PMCid:PMC1283183
Anand, A. C., S. K. Jha, A. Saha, V. Sharma, and C. M. Adya. Thrombosis as a Complication of Extended Stay at High Altitude. National Medical Journal of India 2001; 14 (4).
Bickel, C., R. B. Schnabel, E. Zengin, E. Lubos, H. Rupprecht, K. Lackner, C. Proust, et al. Homocysteine Concentration in Coronary Ar-tery Disease: Influence of Three Common Single Nucleotide Polymorphisms. Nutrition, Metabolism, and Cardiovascular Diseases 2017; 27 (2): 168-75. Doi: https://doi.org/10.1016/j.numecd.2016.09.005 PMid:27773468
Hodis HN, Mack WJ, Dustin L, Mahrer PR, Azen SP, Detrano R, et al. High-dose B vitamin supplementation and progression of sub-clinical atherosclerosis: A randomized controlled trial. Stroke 2009; 40(3):730-6. Doi: https://doi.org/10.1161/STROKEAHA.108.526798 PMid:19118243 PMCid:PMC2701290
Cheriyedath BS, Sc M. Restriction Fragment Length Polymorphism (RFLP) Technique1-5. https://Restriction Fragment Length Polymorphism (RFLP) Technique (news-medical.net).1984.
Mann, N. J., D. Li, A. J. Sinclair, N. P.B. Dudman, X. W. Guo, et al. The Effect of Diet on Plasma Homocysteine Concentrations in Healthy Male Subjects. European Journal of Clinical Nutrition 1999; 53 (11). Doi: https://doi.org/10.1038/sj.ejcn.1600874 PMid:10557004
Rutten-Jacobs, Loes C.A., Matthew T., Poneh A., Vincent T., Cathie S., et al . Association of MTHFR C677T Genotype with Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype." Stroke 2016; 47 (3). Doi: https://doi.org/10.1161/STROKEAHA.115.011545 PMid:26839351 PMCid:PMC4760380
Yakub M, Moti N, Parveen S, Chaudhry B, Azam I, Iqbal M. Polymorphisms in MTHFR, MS and CBS genes and premature acute myo-cardial infarction in a Pakistani population. Pak J Pharm sci 2016; 29 (6):1901-1906. PMID: 28375104
Du, Xiaoxia, Lin Xiao, Rong Sun, Kunpeng Li, Lin Liang, Luping Song, and Zhizhong Liu. n. A Prospective Cohort Study of MTHFR C677T Gene Polymorphism and Its Influence on the Therapeutic Effect of Homocysteine in Stroke Patients with Hyperhomocyste-inemia. BMC Neuro 2020; 20 (1):128. Doi: https://doi.org/10.1186/s12883-020-01701-8 PMid:32278343 PMCid:PMC7149884
Franchis, R. De, I. Fermo, G. Mazzola, G. Sebastio, G. Di Minno, A. Coppola, G. Andria, and A. D'Angelo. Contribution of the Cystathi-onine β-Synthase Gene (844ins68) Polymorphism to the Risk of Early-Onset Venous and Arterial Occlusive Disease and of Fasting Hyperhomocysteinemia. Thrombosis and Haemostasis 2000; 84 (4): 576-82. Doi: https://doi.org/10.1055/s-0037-1614070 PMid:11057853
Toole, James F., M. René Malinow, Lloyd E. Chambless, J. David Spence, L. Creed Pettigrew, Virginia J. Howard, Elizabeth G. Sides, Chin Hua Wang, and Meir Stampfer. Lowering Homocysteine in Patients with Ischemic Stroke to Prevent Recurrent Stroke, Myocardial Infarction, and Death: The Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled Trial. Journal of the American Medical Association 2004; 291 (5): 565-75. Doi: https://doi.org/10.1001/jama.291.5.565 PMid:14762035
Hankey, Graeme J., John W. Eikelboom, Qilong Yi, Kennedy R. Lees, Christopher Chen, et al. Antiplatelet Therapy and the Effects of B Vitamins in Patients with Previous Stroke or Transient Ischaemic Attack: A Post-Hoc Subanalysis of VITATOPS, a Randomised, Pla-cebo-Controlled Trial. The Lancet Neurology 2012; 11 (6): 512-20. Doi: https://doi.org/10.1016/S1474-4422(12)70091-1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Neetu Kataria, Vasantha C Kalyani, Anissa Atif Mirza, Vivekanandhan S, Mritunjai Kumar, Yogesh Bharupi, Shashi Ranjan, Nitesh Kumar, Niraj Kumar
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
The authors retain the copyright of their article, with first publication rights granted to Medsci Publications.