Brain Arteriovenous Malformations are associated with Interleukin-1 Cluster Gene Polymorphisms.

Abstract BACKGROUND: Brain arteriovenous malformations (BAVM) are a rare but important cause of hemorrhagic stroke in young adults. Functional polymorphisms in pro-inflammatory 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<0.001). The carriage of the T allele was related to a 2.47 increased risk of BAVM (CI 95%: 1.72<OR<3.56). Allelic and genotypic frequencies of IL-1RN VNTR were different between cases and controls (p = 0.009). Allele 1 was associated with about twofold increased disease risk (CI 95%: 2.01<OR<5.58). Haplotypes 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 BAVM and influence the clinical characteristics of the disease, supporting a role for pro-inflammatory cytokines in disease etiopathogenesis.