Tumor necrosis factor-alpha gene and cerebral aneurysms

OBJECTIVE: The pathogenesis of intracranial aneurysms is still uncertain. In addition to atherosclerosis, immunological factors may play a role in the disease. Recent studies have suggested that tumor necrosis factor-α (TNF-α), one of the main proinflammatory cytokines, may play a key role in the formation and rupture of cerebral aneurysms. The purpose of this study is to evaluate the association of a functionally active polymorphism (-308 GA) in the TNF-α gene with the risk and the clinical features of aneurysmal subarachnoid hemorrhage. METHODS: A total of 171 consecutive aneurysmal subarachnoid hemorrhage patients and 144 healthy controls were involved in the study. Computed tomographic scan findings were assessed by Fisher grade; clinical neurological assessment was performed using the Hunt and Hess grading system. Patients and controls were genotyped for the- 308 biallelic (GA) polymorphism of the TNF-α gene. RESULTS: The TNF-α G allele was significantly more frequent in patients than in controls (χ2 5.59; P 0.0181) and homozygosity for the G allele, compared with remaining genotypes, was associated with a significantly increased risk of aneurysmal subarachnoid hemorrhage (odds ratio 2.20; 95% confidence interval 1.29odds ratio 3.75). Allelic and genotypic frequencies of the examined polymorphism were not significantly different in disease subgroups. The different TNF-α genotypes do not seem to significantly modify the main clinical features of the disease. CONCLUSION: Our data suggests that the TNF-α gene or a linked locus significantly modulates the risk for aneurysmal subarachnoid hemorrhage. Additional studies in different populations are warranted to confirm our findings.