Background Information

Endothelial nitric oxide synthase (eNOS) gene may be an important candidate enabling the distinction between rupture-prone versus rupture-resistant brain aneurysms (References 1-3, given below). The transcription and translation of this gene ( take me to the Genomics Section now), leads to the production of the protein (enzyme) eNOS, which in turn synthesizes a very important molecule called nitric oxide (NO). NO is a critical mediator of blood vessel function throughout the body, including brain blood vessels (References 4 & 5).

In a study (Reference 3) conducted at the Mayo Clinic in Rochester Minnesota, after receiving informed consent from all participants and with the approval of the Institutional Review Board, a small sample of venous blood was taken from 58 patients diagnosed with ruptured brain aneurysms and 49 patients diagnosed with unruptured brain aneurysms. Genomic DNA was extracted from the white blood cells in these samples, and then a biochemical/genetic assay was developed to screen each sample for the presence of subtle variations ("polymorphisms") in the eNOS gene. The investigators reported that there were genetic differences in the presence of such variations between patients with ruptured compared with unruptured brain aneurysms. The most novel finding of this study was that the presence of two-or-more eNOS gene polymorphisms in a person with a brain aneurysm was somewhere between 8-10 times more likely to be associated with brain aneurysm rupture.

These cerebrovascular eNOS genetic research findings supporting prediction of which brain aneurysm patients might be more susceptible to experiencing rupture of their aneurysm, and which ruptured aneurysm patients might be more susceptible to experiencing cerebral vasospasm ( take me to the Cerebral Vasospasm now), have subsequently been independently supported by the findings of three other research groups in North America (References 6-8). The results appear to be reproducible in Caucasian/"White" but not Asian populations.

What does all this mean for persons with brain aneurysms?

It is hoped that one day, when persons are diagnosed with a brain aneurysm, a small sample of blood can be provided (just like we do for any other blood test) to an appropriate lab for eNOS gene screening. The turnaround for this test (i.e., time between providing a sample and obtaining the result) can be made to be within 24 hrs.

If confirmed, the eNOS gene polymorphism profile of a patient may represent potentially important information that can be used by neurologists and neurosurgeons who may be counseling patients with:

1. UNruptured brain aneurysms regarding observation (as we know that many brain aneurysms can be followed in time) versus earlier treatment; or
2. ruptured brain aneurysms regarding closer monitoring and possible earlier treatment for cerebral vasospasm

Cited References: