Interleukin-1 Cluster Gene Polymorphisms and Aneurysmal Subarachnoid Hemorrhage

Abstract 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-1α, IL-1β, 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-1α (−889), IL-1β (-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-1β 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. CONCLUSION 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-1β gene may modify disease severity and may be regarded as disease severity gene.