Interleukin-1 cluster gene polymorphisms and aneurysmal subarachnoid hemorrhage.
BACKGROUND
Emerging data indicate that proinflammatory cytokines may be involved in the pathogenesis of intracranial aneurysms. Interleukin (IL)-1 is a proinflammatory cytokine that plays a pivotal role in both acute and chronic central nervous system injuries.


OBJECTIVE
To investigate whether select polymorphisms in the IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes are associated with both susceptibility to and clinical characteristics of subarachnoid hemorrhage due to intracranial aneurysm rupture.


METHODS
Allelic and genotypic frequencies of the IL-1alpha (-889), IL-1beta (-511), and IL-1 receptor antagonist (VNTR) genes were determined in 215 patients and 155 healthy controls. Patient files were reviewed for the clinical characteristics at hospital admission and at 6-month follow-up.


RESULTS
No association between aneurysmal subarachnoid hemorrhage susceptibility and the examined cytokine gene polymorphisms was found. Haplotype analysis did not show any significant difference between cases and controls. However, aneurysmal subarachnoid hemorrhage patients carrying the T/T genotype of the IL-1beta gene showed a significant (P = .034) increase in the Hunt and Hess scores at hospital admission and a significant (P = .026) reduction in 6-month Glasgow Outcome Scale scores. The remaining polymorphisms showed no effect on the clinical features examined.


CONCLUSIONS
Our results do not support the hypothesis that genetic variation in select polymorphisms of the IL-1 cluster genes is associated with aneurysmal subarachnoid cerebral hemorrhage. However, the IL-1beta gene may modify disease severity and may be regarded as disease severity gene.
Fontanella
Marco
M
Division of Neurosurgery, Department of Neuroscience, University of Torino, Torino, Italy. marco.fontanella@tin.it
Rainero
Innocenzo
I
Gallone
Salvatore
S
Rubino
Elisa
E
Fornaro
Riccardo
R
Fenoglio
Pierpaola
P
Valfrè
Walter
W
Vaula
Giovanna
G
Benevello
Chiara
C
Ducati
Alessandro
A
Pinessi
Lorenzo
L
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000276:immunology; D005838:Genotype; D023261:Glasgow Outcome Scale; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1