The Correlation of Endothelial Nitric Oxide Synthase (eNOS) Polymorphism and Other Risk Factors with Aneurysmal Subarachnoid Hemorrhage: A Case-Control Study

摘要

Objective: Endothelial nitric oxide synthase gene (eNOS) polymorphism is an association with cerebral aneurysm formation, rupture, and vasospasm and plays a role in the a functional outcome. Patients and Methods: The aim of the study was to evaluate the role of eNOS gene polymorphism and further assess the predictors of outcome in the aneurysmal subarachnoid hemorrhage (aSAH). A prospective case-control study was conducted from 2009 to 2012 among those who presented with aSAH. A serum sample was collected from aSAH patients along with age and sex-matched healthy controls. The frequency of polymorphism of eNOS gene and other factors (demographic and aneurysmal) were correlated with functional outcome at six month of follow-up. Results: 100 patients with aSAH and 100 healthy controls were enrolled in the cohort. The mean age of the patient group was 51.61 years and control group was 45.81 years with a male:female ratio of 1:1.38 and 1:1.08 for patients and controls, respectively. Among all eNOS polymorphisms, 4BB (65%) 24-VNTR, TT (71%) of T-786C, and GG (71%) of G947T were the most common and frequency was similar in the control group. The occurrences of hypertension, smoking, diabetes were 32%, 37%, and 7% respectively in the patient group. Maximum patients were in WFNS grade 1 (53%) followed by 23% grade 2 and only 10% in grade 4. Fisher grade 3 (57%) was the most common followed by Fisher grade 4 (28%). Most aneurysms (97%) were in anterior circulation. 83% of the aneurysms were clipped and 10% underwent coiling. Size-wise most of the aneurysms were in the middle group (6–9 mm) followed by bigger group (10 mm) (37%); only 6% aneurysms were in the small aneurysm (6 mm) group. 33% of the patients had evidence of vasospasm. TT of G894T polymorphism (60%) had the highest incidence of vasospasm. Univariate analysis showed smoking (OR: 3.19, CI: 1.19–8.84, P = 0.01), 4AA (OR: 12.15, CI: 1.13–624.9, P = 0.03) variety of 24-VNTR polymorphism, CC (OR: 15.39, CI: 1.60–762.8, P = 0.01) variety of T786C polymorphism, Fisher grade 4 (OR: 3.43, CI: 1.24–9.68, P = 0.01), WFNS grade (poor vs. good) (OR: 3.42, CI: 1.17–10.12, P = 0.02), vasospasm (OR: 3.84, CI: 1.42–10.75, P = 0.006), intraoperative rupture (OR: 4.77, CI: 1.55–15.27, P = 0.004) were significantly related with unfavorable outcome at 6 months follow-up. In regression analysis, smoking (CI: 0.06–0.69, P = 0.01), Fisher grade 4 (CI: 0.09–1.00, P = 0.05), and intraoperative rupture (CI: 0.05–0.89, P = 0.03) were correlated with an unfavorable outcome at 6 months follow-up. Conclusion: The eNOS gene polymorphism, smoking, clinical grade (WFNS), Fisher grade, intraoperative rupture, and vasospasm play a role in functional outcome after the treatment of cerebral aneurysms.