The endothelial nitric oxide synthase (eNOS) encoded by the NOS3 gene is responsible for the
synthesis of a vasoactive endothelium-derived nitric oxide (NO). The genetic
polymorphism of this gene explains, in part, why some people are prone to
develop stroke than others. In this study we conducted a case control study in
Bahrainis to investigate “for the first time” the relationship between NOS3 894G> T (rs1799983) and 786T> C (rs2070744) polymorphisms with the stroke predisposition in Bahraini
population. Detection of NOS3
polymorphism was performed by PCR RFLP genotyping method. The level of NO among
cases and controls was measured using ELISA. A total of 93 unrelated stroke
patients and 86 controls were included in the study. The three types of stroke;
Ischemic, hemorrhagic and transient ischemic attack were reported (91.4%, 7.5%
and 1.1% respectively). No significant gender difference was observed (P = 0.74). Having previous stroke was a
highly significant risk factor of the disease (P = 0.001, OR = 1.4), where as a family history of stroke was not
(OR = 0.11). The analysis provides evidence that the mutant 894GT+ TT
genotypes of NOS3 894G> T polymorphism were positively associated with stroke predisposition and
it increased the risk of
References
[1]
Lackland, D.T., Roccella, E.J., Deutsch, A.F., et al. (2014) Factors Influencing the Decline in Stroke Mortality: A Statement from the American Heart Association/American Stroke Association. Stroke, 45, 315-353.
https://doi.org/10.1161/01.str.0000437068.30550.cf
[2]
Sacco, R.L., Wolf, P.A. and Gorelick, P.B. (1999) Risk Factors and Their Management for Stroke Prevention, Outlook for 1999 and Beyond. Neurology, 53, S15-S24.
https://doi.org/10.1212/WNL.53.7.15A
[3]
Benamer, H.T. and Grosset, D. (2009) Stroke in Arab Countries: A Systematic Literature Review. Journal of the Neurological Sciences, 284, 8-23.
https://doi.org/10.1016/j.jns.2009.04.029
[4]
Go, A.S., Mozaffarian, D., Roger, V.L., et al. (2013) Heart Disease and Stroke Statistics—2013 Update: A Report from the American Heart Association. Circulation, 127, e6-e245. https://doi.org/10.1161/CIR.0b013e31828124ad
[5]
Al Banna, M., Baldawi, H., Kadhim, A., Humaidan, H. and Whitford, D.L. (2015) Stroke in Bahrain: Rising Incidence, Multiple Risk Factors, and Suboptimal Care. International Journal of Stroke, 10, 615-618. https://doi.org/10.1111/ijs.12513
[6]
Al-Jishi, A.A. and Mohan, P.K. (2000) Profile of Stroke in Bahrain. Neurosciences (Riyadh), 5, 30-34.
[7]
Flossmann, E., Schulz, U.G. and Rothwell, P.M. (2004) Systematic Review of Methods and Results of Studies of the Genetic Epidemiology of Ischemic Stroke. Stroke, 35, 212-227. https://doi.org/10.1161/01.STR.0000107187.84390.AA
[8]
Razvi, S.S. and Bone, I. (2006) Single Gene Disorders Causing Ischaemic Stroke. Journal of Neurology, 253, 685-700. https://doi.org/10.1007/s00415-006-0048-8
[9]
John, F., Senthil, R. and Pradeep, K. (2007) The Role of Genetics in Stroke. International Journal of Stroke, 83, 590-595. https://doi.org/10.1136/pgmj.2007.060319
[10]
James, F.M., Bradford, B.W. and Stephen, S.R. (2011) Genetic Susceptibility to Ischemic Stroke. Nature Reviews Neurology, 7, 369-378.
https://doi.org/10.1038/nrneurol.2011.80
[11]
Pezzini, A. (2012) Genetic Determinants of Juvenile Stroke. Thrombosis Research, 129, 330-335.
[12]
Ignarro, L.J., Buga, G.M., Wood, K.S., Byrns, R.E. and Chaudhuri, G. (1987) Endothelium-Derived Relaxing Factor Produced and Released from Artery and Vein Is Nitric Oxide. Proceedings of the National Academy of Sciences of the United States of America, 84, 9265-9269
[13]
Riddell, D.R. and Owen, J.S. (1999) Nitric Oxide and Platelet Aggregation. Vitamins and Hormones, 57, 25-48.
[14]
van Goor, H., Albrecht, E.W., Heeringa, P., et al. (2001) Nitric Oxide Inhibition Enhances Platelet Aggregation in Experimental Anti-Thy-1 Nephritis. Nitric Oxide, 5, 525-533. https://doi.org/10.1006/niox.2001.0382
[15]
Kurose, I., Kubes, P., Wolf, R., et al. (1993) Inhibition of Nitric Oxide Production. Mechanisms of Vascular Albumin Leakage. Circulation Research, 73, 164-171.
https://doi.org/10.1161/01.RES.73.1.164
[16]
Endres, M., Laufs, U., Liao, J.K. and Moskowitz, M.A. (2004) Targeting eNOS for Stroke Protection. Trends Neurosciences, 27, 283-289.
https://doi.org/10.1016/j.tins.2004.03.009
[17]
Munafo, M.R. and Flint, J. (2004) Meta-Analysis of Genetic Association Studies. Trends Genetics, 20, 439-444. https://doi.org/10.1016/j.tig.2004.06.014
[18]
Dutra, A.V., Lin, H.-F., Juo, S.-H., et al. (2006) Analysis of the Endothelial Nitric Oxide Synthase Gene as a Modifier of the Cerebral Response to Ischemia. Journal of Stroke, 15, 128-131.
[19]
Wang, M.Y., Jiang, X.B., Wu, W.L. and Zhang, D.F. (2013) Endothelial NO Synthase Gene Polymorphisms and Risk of Ischemic Stroke in Asian Population: A Meta-Analysis. PLoS ONE, 8, e60472.
[20]
Kang, M.K., Kim, O.J., Jeon, Y.J., Kim, H.S., et al. (2014) Interplay between Polymorphisms in the Endothelial Nitric Oxide Synthase (eNOS) Gene and Metabolic Syndrome in Determining the Risk of Ischemic Stroke in Koreans. Journal of Neurological Sciences, 344, 55-59. https://doi.org/10.1016/j.jns.2014.06.020
[21]
Census Summary Result (2010) Population, Housing, Buildings, Establishments and Agriculture Census.
http://www.cio.gov.bh/CIO_ARA/English/Publications/Census/2011%2009%2018%20Final% 20English%20Census%202010%20Summary%20%20Results%20-%20Review%201.pdf
[22]
Al Arrayed, S.S. Genetic Diseases in Bahrain. Genetic Disorders in the Arab World.
http://www.academia.edu/763838/Genetic_Diseases_in_Bahrain
[23]
Meschia, J.F., Worrall, B.B. and Rich, S.S. (2011) Genetic Susceptibility to Ischemic Stroke. Nature Reviews, Neurology, 7, 369-378.
https://doi.org/10.1038/nrneurol.2011.80
[24]
Loo, K.W., Heidi, S., Anthony, A., Emily, C., Larisa, M.H., Siew, H.G. and Lyn, R.G. (2015) A Potential Epigenetic Marker Mediating Serum Folate and Vitamin B12 Levels Contributes to the Risk of Ischemic Stroke. BioMed Research International, 2015, Article ID 167976. http://doi.org/10.1155/2015/167976
[25]
Radomski, M.W., Palmer, R.M. and Moncada, S. (1987) Endogenous Nitric Oxide Inhibits Human Platelet Adhesion to Vascular Endothelium. The Lancet, 330, 1057-1058. https://doi.org/10.1016/S0140-6736(87)91481-4
[26]
Della-Morte, D., Guadagni, F., Palmirotta, R., et al. (2012) Genetics of Ischemic Stroke, Stroke-Related Risk Factors, Stroke Precursors and Treatments. Pharmacogenomics, 13, 595-613. https://doi.org/10.2217/pgs.12.14
[27]
Morris, C.M., Ballard, C.G., Allan, L., Rowan, E., Stephens, S., Firbank, M., Ford, G.A., Kenny, R.A., O’Brien, J.T. and Kalaria, R.N. (2011) NOS3 Gene rs1799983 Polymorphism and Incident Dementia in Elderly Stroke Survivors. Neurobiology of Aging, 32, 554.e1-554.e6. https://doi.org/10.1016/j.neurobiolaging.2010.06.012
[28]
Green, D.J. (2009) Exercise Training as Vascular Medicine: Direct Impacts on the Vasculature in Humans. Exercise and Sport Sciences Reviews, 37, 196-202.
[29]
Abdul Rahman, O.M. (1998) Change in Dietary Habits, Lifestyle and Trend in Diseases in the GCC Countries. Bahrain Medical Bulletin, 20, 87-90.