TUMOR NECROSIS FACTOR-α 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 polymor- phism (-308 GA) in the TNF-α gene with the risk and the clinical features of aneurys- mal subarachnoid hemorrhage. METHODS: A total of 171 consecutive aneurysmal subarachnoid hemorrhage patients and 144 healthy controls were involved in the study. Computed tomographic scan find- ings 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 con- trols (χ 2 � 5.59; P � 0.0181) and homozygosity for the G allele, compared with remain- ing genotypes, was associated with a significantly increased risk of aneurysmal sub- arachnoid hemorrhage (odds ratio � 2.20; 95% confidence interval � 1.29� odds 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 dif- ferent populations are warranted to confirm our findings.