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.
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.
Authors: Nikolaos Mouchtouris; Pascal M Jabbour; Robert M Starke; David M Hasan; Mario Zanaty; Thana Theofanis; Dale Ding; Stavropoula I Tjoumakaris; Aaron S Dumont; George M Ghobrial; David Kung; Robert H Rosenwasser; Nohra Chalouhi Journal: J Cereb Blood Flow Metab Date: 2014-11-19 Impact factor: 6.200
Authors: Shantel Weinsheimer; Ari D Brettman; Ludmila Pawlikowska; D Christine Wu; Michael R Mancuso; Frank Kuhnert; Michael T Lawton; Stephen Sidney; Jonathan G Zaroff; Charles E McCulloch; William L Young; Calvin Kuo; Helen Kim Journal: Transl Stroke Res Date: 2012-08-14 Impact factor: 6.829
Authors: Shantel Weinsheimer; Nasrine Bendjilali; Jeffrey Nelson; Diana E Guo; Jonathan G Zaroff; Stephen Sidney; Charles E McCulloch; Rustam Al-Shahi Salman; Jonathan N Berg; Bobby P C Koeleman; Matthias Simon; Azize Bostroem; Marco Fontanella; Carmelo L Sturiale; Roberto Pola; Alfredo Puca; Michael T Lawton; William L Young; Ludmila Pawlikowska; Catharina J M Klijn; Helen Kim Journal: J Neurol Neurosurg Psychiatry Date: 2016-01-27 Impact factor: 10.154