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-alpha (TNF-alpha), 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 G<A) in the TNF-alpha 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 (G<A) polymorphism of the TNF-alpha gene.


RESULTS
The TNF-alpha G allele was significantly more frequent in patients than in controls (chi2 = 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 = 1.29<odds ratio<3.75). Allelic and genotypic frequencies of the examined polymorphism were not significantly different in disease subgroups. The different TNF-alpha genotypes do not seem to significantly modify the main clinical features of the disease.


CONCLUSIONS
Our data suggests that the TNF-alpha gene or a linked locus significantly modulates the risk for aneurysmal subarachnoid hemorrhage. Additional studies in different populations are warranted to confirm our findings.
Fontanella
Marco
M
Department of Neuroscience, Division of Neurosurgery, University of Turin, Turin, Italy. marco.fontanella@tin.it
Rainero
Innocenzo
I
Gallone
Salvatore
S
Rubino
Elisa
E
Fenoglio
Pierpaola
P
Valfrè
Walter
W
Garbossa
Diego
D
Carlino
Christian
C
Ducati
Alessandro
A
Pinessi
Lorenzo
L
D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D002532:Intracranial Aneurysm / Q000453:epidemiology* / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha