Background: Brain arteriovenous malformations (BAVMs) are a rare but important cause of hemorrhagic stroke in young adults. Functional polymorphisms in proinflammatory cytokines have been associated with various cerebrovascular phenotypes, including ischemic stroke, aneurysmal subarachnoid hemorrhage, and BAVM.
Objective: To investigate whether functional polymorphisms in the IL-1α, IL-1β, and IL-1RN genes are associated with both susceptibility and clinical characteristics in BAVM patients.
Methods: Allelic and genotypic frequencies of IL-1α (-889 C>T), IL-1β (-511 C>T), and IL-1RN (VNTR) polymorphisms were analyzed in 101 unrelated BAVM patients and in 210 healthy subjects. Main clinical characteristics of the disease were compared according to different genotypes.
Results: Both allelic and genotypic frequencies of IL-1α -889 C>T showed a significant association with BAVM (P < .001). The carriage of the T allele was related to a 2.47 increased risk of BAVM (odds ratio, 2.47; 95% confidence interval: 1.72-3.56). Allelic and genotypic frequencies of IL-1RN VNTR were different between cases and controls (P = .009). Allele 1 was associated with about a twofold increased disease risk (95% confidence interval: 2.01-5.58). Haplotype analyses confirmed these findings. Several clinical characteristics of the disease were significantly modified by IL-1α and IL-1β genotypes.
Conclusion: Our data suggest that functional polymorphisms within the IL-1 complex gene are associated with BAVMs and influence the clinical characteristics of the disease, supporting a role for proinflammatory cytokines in disease etiopathogenesis.