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|Year : 2020 | Volume
| Issue : 1 | Page : 84-85
Association of Genetic Polymorphisms in Tumor Necrosis Factor-Alpha gene with the risk of Intracerebral Hemorrhage in North Indian Population
Nitin Yadav1, Jyotirmoy Banerjee2, Manjari Tripathi3, P Sarat Chandra4, Aparna B Dixit1
1 Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi; Center of Excellence for Epilepsy, AIIMS, New Delhi, India
2 Center of Excellence for Epilepsy; Department of Biophysics, AIIMS, New Delhi, India
3 Center of Excellence for Epilepsy; Department of Neurology, AIIMS, New Delhi, India
4 Center of Excellence for Epilepsy; Department of Neurosurgery, AIIMS, New Delhi, India
|Date of Web Publication||28-Feb-2020|
Dr. Aparna B Dixit
104, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Yadav N, Banerjee J, Tripathi M, Chandra P S, Dixit AB. Association of Genetic Polymorphisms in Tumor Necrosis Factor-Alpha gene with the risk of Intracerebral Hemorrhage in North Indian Population. Neurol India 2020;68:84-5
|How to cite this URL:|
Yadav N, Banerjee J, Tripathi M, Chandra P S, Dixit AB. Association of Genetic Polymorphisms in Tumor Necrosis Factor-Alpha gene with the risk of Intracerebral Hemorrhage in North Indian Population. Neurol India [serial online] 2020 [cited 2020 Mar 28];68:84-5. Available from: http://www.neurologyindia.com/text.asp?2020/68/1/84/279683
Intracerebral Hemorrhage (ICH) refers to the bleeding in the intracranial vault, meninges, and also the brain parenchyma. Microglia are the inhabiting immune cells in the brain. An injury to the brain results in the activation of these microglial cells. Various states of modulation of microglia can have either neurotoxic or neuroprotective effect. An inflammatory molecule tumor necrosis factor-alpha (TNF-alpha) derived from activated microglia has not only been shown to induce the production of other inflammatory molecules but also as an autocrine mediator in microglial activation in response to traumatic brain injury (TBI) and spinal cord injury (SCI)., Alteration in the TNF-alpha expression has been associated with cerebral aneurysms and subarachnoid hemorrhage but no direct role has been established., There are limited reports on investigation of the association between TNF-α gene polymorphism and the risk of hemorrhagic stroke in multiple ethnicities. Ruigrok et al. have evaluated the role of APOE, IGF-1, TNF-alpha among other genes in subarachnoid hemorrhage, which has established the role of TNF-alpha as a high risk factor. The pathway by which TNF-alpha cause ICH is yet to be identified.
In this case-control genetic association study, Kumar et al. have reported four polymorphic regions (-308G/A, +488G/A, -857C/T, and -1031T/C) in the promoter region of TNF-α gene in north Indian population. The authors established an independent association of TNF-α +488G/A gene polymorphism with the risk of ICH, while the other three SNP's were not found to be associated with the risk of ICH. The 3 SNPs -308, -857, and -1031 found in this study were earlier reported to be associated with spontaneous deep intracerebral hemorrhage in Taiwanese population with a larger sample size while establishing a gender association of these SNPs with the disease, while this issue has not explored the gender association of these SNPs in ICH. Various other studies have shown that polymorphisms at position -308 and -863 in the promoter region of the TNF-α gene were associated with risks of subarachnoid haemorrhage (SAH) in multiple ethnicities.,
A particularly important finding in this study is the SNP +488G/A in the promoter region of TNF-alpha which was found to be independently associated with the risk of ICH under dominant [GG + GA vs AA] and allelic [G vs A] models. Although this is the first study in the North Indian population, the authors have not laid light on the ethnic correlation with the progression of the disease. Further studies on protein and mRNA analysis of TNF-alpha in the ICH patients and controls will be helpful in elucidating the possible mechanisms of these SNPs in modulating the expression of TNF-alpha levels in these patients and its association with the risk of ICH.
| » References|| |
Caceres JA, Goldstein JN. Intracranial haemorrhage. Emerg Med Clin North Am 2010;30:771-94.
Longhi L, Perego C, Ortolano F, Aresi S, Fumagalli S, Zanier ER, et al
. Tumor necrosis factor in traumatic brain injury: Effects of genetic deletion of p55 or p75 receptor. J Cereb Blood Flow Metab 2013;33:1182-9.
Akhmetzyanoval E, Kletenkov K, Mukhamedshina1 Y, Rizvanov A. Different approaches to modulation of microglia phenotypes after spinal cord injury. Front Syst Neurosci 2019;13:37.
Lei B, Dawson HN, Roulhac-Wilson B, Wang H, Laskowitz DT, James ML. Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral haemorrhage. J Neuroinflamm 2013;10:103.
Li G, Wang QS, Lin TT. Alterations in the expression of protease-activated receptor 1 and tumor necrosis factor-α in the basilar artery of rats following subarachnoid haemorrhage. Exp Ther Med 2016;11:717-22.
Ruigrok YM, Slooter AJ, Bardoel A, Frijns CJ, Rinkel GJ, Wijmenga C. Genes and outcome after aneurysmal subarachnoid haemorrhage. J Neurol 2005;252:417-22.
Chen Y, Hu F, Chen P, Wu YR, Wu HC, Chen ST, et al
. Association of TNF-α gene with spontaneous deep intracerebral haemorrhage in the Taiwan population: A case-control study. BMC Neurol 2010;10:41.
Fontanella M, Rainero I, Gallone S, Rubino E, Fenoglio P, Valfrè W, et al
. Tumor necrosis factor-α gene and cerebral aneurysms. Neurosurgery 2007;60:668-72; discussion 672-3.
Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S, Kato K, et al
. Genetic risk for ischemic and hemorrhagic stroke. Arterioscler Thromb Vasc Biol 2006;26:1920-5.