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|Year : 2019 | Volume
| Issue : 4 | Page : 1013-1014
eNOS: A Passing Fad or the Crux of the Panacea?
Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||10-Sep-2019|
Dr. Sivashanmugam Dhandapani
Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Dhandapani S. eNOS: A Passing Fad or the Crux of the Panacea?. Neurol India 2019;67:1013-4
I congratulate Konar SK, Ramesh S, Christopher R, Prasanthi A, Bhat DI, Shukla D, et al. The correlation of endothelial nitric oxide synthase (eNOS) polymorphism and other risk factors with aneurysmal subarachnoid hemorrhage: A case-control study. Neurol India 2019;67:1006-12.
Nitric oxide (NO), a vascular signaling molecule and immune effector has garnered much attention since 1998 when it was recognized with a Nobel prize in physiology or medicine. Endothelial nitric oxide synthase (eNOS) is one of the three isoforms of the enzyme responsible for the generation of NO in the vascular endothelium. eNOS polymorphisms have been implicated in a wide spectrum of pathology, ranging from vascular disorders such as stroke and aneurysmal subarachnoid hemorrhage (aSAH); lifestyle disease combinations such as metabolic syndrome; immune-inflammatory processes such as systemic lupus erythematosus; and, even multifactorial ailments such as cancer and schizophrenia.,, The NIMHANS study identifies polymorphisms in the eNOS gene to be similar among patients of aSAH and controls, with 4AA of 24VNTR and CC of T786C polymorphisms having a significant association with Glasgow Outcome Scale. However, the effect of these gene polymorphisms were not independent of other factors. Moreover, TT of G894T polymorphism was most associated with vasospasm.
The molecular substrates responsible for an unfavorable neurological outcome after aSAH, though similar in nature to head injury, have in addition, vasospasm, a condition puzzling not merely in its pathophysiology but also in terminology as well as in its proportional burden on the outcome., We had previously reported on MTHFR polymorphisms and a complex interplay of metabolic aberrations, inflammation and nutritional load in aSAH leading to a 'reverse epidemiology paradox'., Many parameters in aSAH have been noted in various studies to have a significant association with either of the factors including angiographic vasospasm, delayed cerebral ischemia (DCI), neurological outcome or cognitive deficits, but this association is seldom in congruity.,, It is still not lucid why there is a disparity between the impact of radiologic and clinical vasospasm on the overall clinical outcome. Unless the prognostic link between a substrate, clinico-radiological phenomena and outcome is complete with coherent reasoning, the association remains controversial.
The role of NO and eNOS polymorphisms in aSAH is as intriguing as its plethora of disease associations.,, Studies have even shown the T786C polymorphism to be associated with the development of aneurysms, in contrast to the similarity with the control group in the NIMHANS study. While other studies on aSAH have noted a significant association of 4AA of 24VNTR and CC of T786C polymorphisms with DCI and cardiac instability, none have shown an independent association with the neurological outcome. This may probably be due to a combination of the following reasons:First, eNOS polymorphisms may be associated with more serious early brain injury induced by aSAH, thereby decreasing the threshold of vasospasm, leading to a poorer outcome. Second, it may have a role in shared biochemical mechanisms of cytotoxicity common to many other diseases. Third, it may be a mere bystander of the confounding metabolic derangements which worsen outcome after aSAH.
Although the direct causality or specificity of eNOS polymorphisms on the outcome after aSAH is not known, we may still utilize these polymorphisms in clinical practice, by identifying high-risk patients who may benefit from proactive management. Thus, an unfavorable outcome may be preventable. As the pharmacogenetic studies focusing on eNOS polymorphisms have shown promise in predicting the therapeutic response of medications such as statins and phosphodiesterase inhibitors, it is even possible that supportive and definitive management of aneurysms in the future may be tailored according to the eNOS genomics. We need collaboration between neurosurgeons, radiologists, geneticists, epidemiologists, and statisticians to design good multicenter trials to bring out evidence whether eNOS polymorphism is merely a passing fad in the management of aSAH or is the crux of the panacea, the beneficial effects of which may be extending to other diseases as well.
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Conflicts of interest
There are no conflicts of interest.
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