Role of NOS3 894G>T Gene Polymorphism in Traumatic Cerebral Hemorrhagic Contusion Khartoum, Sudan, 2020-2021

Download Article

DOI: 10.21522/TIJAR.2014.10.01.Art005

Authors : SAMAH ABDELRAHMAN HASSAN IBRAHIM, Zeinab Swar Eldahab

Abstract:

The nitric oxide produced by the endothelial nitric synthase (NOS3) gene helps to maintain cerebral blood flow (CBF) after traumatic brain injuries (TBI). The aim is to determine the prognostic role of NOS3 894 G>T gene in traumatic hemorrhagic contusion and outcome. A cross-sectional study was conducted for 90 patients who attended the National Centre for Neurological Sciences, Khartoum, Sudan. Non-Sudanese patients, hemorrhagic contusions associated with other types of brain bleeding, and patients with chronic disease were excluded. An initial CT scan was used upon admission to detect brain edema, anatomical site, and the number of contusions. The Glasgow coma scale (GCS) was used upon admission to assess the trauma severity. The Glasgow outcomes scale (GOS) was used upon discharge to assess the outcome. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for NOS3 genotyping. The result shows that 93.3% of patients were male, while 32.2% of them were female. It further indicates that 58.9 % had a mild injury; 60% of the patients were presented with frontal lobe injury, 14.4% had multiple sites injury, and 22.2% had brain edema. The number of deaths was 8 (8.9%). The genotyping of NOS3 revealed that 94.4% of patients had homozygous GG and 5.6% heterozygous GT. G allele represented 97.2% of NOS3 alleles. NOS3 894 G>T genotypes were not significantly associated with patients, linguistic afflation’ and outcome. The study concluded that NOS3 894G>T gene has no prognostic role in traumatic hemorrhagic contusion and outcome.

Keywords: Nitric oxide synthase gene, Traumatic brain injury, Glasgow coma scale, Glasgow outcomes scale.

References:

[1] Alahmadi, H., Vachhrajani, S., and Cusimano M., 2010, The natural history of brain contusion: an analysis of radiological and clinical progression. J Neurosurg,112(5),1139-1145, https://doi.org/10.3171/2009.5.JNS081369.

[2] Kurland, D., Hong, C., Aarabi, B., Gerzanich, V., and Simard, J. M., 2012, Hemorrhagic Progression of a Contusion after Traumatic Brain Injury: A Review. J Neurotrauma,29(1),19-31, https://www.liebertpub.com/doi/10.1089/neu.2011.2122.

[3] Hassan, S. A., Gassoum, A.F., Aldeaf, S.A., Arbab, M.A., and Musa, H. H., 2020, Association between Acute Inflammatory Cells and Mutation in ICAM-1 gene with Injury Severity and Outcome among Traumatic Cerebral Hemorrhagic Contusion. J Acute Med ,10(1),1-8, https://pubmed.ncbi.nlm.nih.gov/32995149/.

[4] Hassan, S.A., Arbab, M.A., and Musa, H.H., 2020, Association of RETN -420 C/G genotypes with CRP, Brain edema, GCS, and GOS among Traumatic Cerebral Hemorrhagic Contusion. J Emerg Med Trauma Acute Care,2020(1), https://doi.org/10.5339/jemtac.2020.4.

[5] Hassan, S.A., Arbab, M.A., Abdelrahman, S.F., Aldeaf, S.A., Gassoum, A.F.,and Musa, H.H, 2020, The significance of mutation in IL-1B gene and circulatory level for prediction of trauma severity and outcome in Traumatic Cerebral Hemorrhagic Contusion. J Acute Med,10(2),70-76, https://pubmed.ncbi.nlm.nih.gov/32995158/.

[6] Kondkar, A.A., Azad, T.A., Sultan, T., Osman, E.A., Almobarak, F.A., Al-Obeidan, S.A., 2020, Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open- angle glaucoma in a Saudi cohort. Plos One,15(1),e0227417,https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227417

[7] Geller, D.A., Lowenstein, C.J., Shapiro, R.A., Nussler, A.K., Di Silvio, M., Wang, S.C., Nakayama, D. K., Simmons, R.L., Snyder, S.H., and Billiar, T.R., 1993, Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. PNAS, 90(8),34913495,https://doi.org/10.1073/pnas.90.8.3491.

[8] Nasyrova, R.F., Moskaleva, P.V., Vaiman, E.E., Shnayder, N.A., Blatt, N.L.,and Rizvanov, A.A., 2020, Genetic Factors of Nitric Oxide’s System in Psychoneurologic Disorders. Int J Mol Sci,21(5),1604,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084194/.

[9] Hancock, D.B., Martin, E.R., Vance, J.M.,and Scott, W.K., 2008, Nitric oxide synthase genes and their interactions with environmental factors in Parkinson’s disease. Neurogenetics, 9(4), 249–262, https://link.springer.com/article/10.1007/s10048-008-0137-1.

[10] Marsden, P.A., Heng, H.H., Scherer, S.W., Stewart, R.J., Hall, A.V., Shi, X.M., Tsui, L.C., and Schappert, T.K., 1993, Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem, 268(23),17478-17488, https://pubmed.ncbi.nlm.nih.gov/7688726/.

[11] Robertson, C.S., Gopinath, S.P., Valadka, A.B., Van, M., Swank, P.R., and Goodman, J.C., 2011, Variants of the Endothelial Nitric Oxide Gene and Cerebral Blood Flow after Severe Traumatic Brain Injury. J Neurotruma, 28(5),727-737, https://pubmed.ncbi.nlm.nih.gov/21332418/.

[12] Nassereddine, S., Idrissi, H.H., Habbal, R., Abouelfath, R., Korch, F., Haraka. M., Karkar, A., and Nadifi, S., 2018, The polymorphism G894 T of endothelial nitric oxide synthase (eNOS) gene is associated with susceptibility to essential hypertension (EH) in Morocco. BMC Medical Genetics, 19(1),127. https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-018-0638-1.

[13] Luo, Z., Jia, A., Lu, Z., Muhammad, I., and Adenrele, A., Song, Y., 2019, Associations of the NOS3 rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis. Postgrad Med J, 95(1125), 361-371, https://pmj.bmj.com/content/95/1125/361.

[14] Ahn, M.J., Sherwood, E.R., Prough, D.S., Lin, C.Y., and DeWitt, D.S., 2004, The effects of traumatic brain injury on cerebral blood flow and brain tissue nitric oxide levels and cytokine expression. J Neurotrauma,21(10),1431-1442, https://www.liebertpub.com/doi/10.1089/neu.2004.21.1431.

[15] Harish, G., Mahadevan, A., Pruthi, N., Sreenivasamurthy, S., Puttamallesh, V., Prasad, T. S., Shankar, S. K., and Bharath, M., 2015, Characterizations of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and per contusion. J Neurochemistry, 134(1), 156-172, https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.13082.

[16] https://www.qiagen.com/us/products/discovery-and-translational-research/dna-rna-purification/dnapurification/genomic-dna/qiawave-dna-kits/

[17] Veenith, T., Goon, S.H., and Burnstein, R.M., 2009, Molecular mechanisms of traumatic brain injury: the missing link in management. World J Emerg Surg , 4(1), 7-10, https://wjes.biomedcentral.com/articles/10.1186/1749-7922-4-7.

[18] Dardiotis, E., Foutas, K.N., Dardioti, M., Xiromerisiou, G., Kapsalaki, E., Tasiou, A., and Hadjigeorgiou, G. M.,2010, Genetic association studies in patients with traumatic brain injury. Neurosurg Focus, 28 (1), E 9, https://doi.org/10.3171/2009.10.FOCUS09215.

[19] Tanus-Santos, J.E., Desai, M., and Flockhart, D.A., 2001, Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. Pharmacogenetics, 11(8), 719-725, https://pubmed.ncbi.nlm.nih.gov/11692081/.

[20] Davidson, J, Cusimano, M. D., and Bendena, W,G., 2015, Post-Traumatic Brain Injury: Genetic Susceptibility to Outcome. Neuroscientist, 21(4), 424-41, https://pubmed.ncbi.nlm.nih.gov/25059577/.