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  • Title: IL1B and VWF variants are associated with fibrinolytic early recanalization in patients with ischemic stroke.
    Author: Fernández-Cadenas I, Del Río-Espínola A, Giralt D, Domingues-Montanari S, Quiroga A, Mendióroz M, Ruíz A, Ribó M, Serena J, Obach V, Freijo MM, Martí-Fábregas J, Delgado P, Montaner J.
    Journal: Stroke; 2012 Oct; 43(10):2659-65. PubMed ID: 22858724.
    Abstract:
    BACKGROUND AND PURPOSE: There is a great interindividual variability among patients with acute ischemic stroke regarding the response to intravenous tissue-type plasminogen activator treatment. The aim of this study was to identify genetic variants associated with recanalization, and thus treatment efficacy, after tissue-type plasminogen activator administration. METHODS: A total of 140 single nucleotide polymorphisms from 97 candidate genes were successfully genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited tissue-type plasminogen activator-treated patients, of whom 33% recanalized during tissue-type plasminogen activator infusion. Functional studies were then performed, including assessment of interleukin 1B mRNA levels and von Willebrand factor, FIII, FVII, FVIII, and FX protein activity. RESULTS: After replication, the following single nucleotide polymorphisms were associated with early recanalization: rs1143627 in IL1B gene (CC: 53.1% of recanalization, A-carriers: 32.7%; P=0.022; replication cohort: P=0.046), rs16944 in IL1B gene (AA: 50% of recanalization, G-carriers: 32%; P=0.038; replication cohort: P=0.049), and rs1063856 in the vWF gene (GG: 53.8% of recanalization, A-carriers: 31.5%; P=0.006; replication cohort: P=0.046). The functional studies revealed an association between the rs1063856 single nucleotide polymorphisms in vWF and FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%; P=0.005). CONCLUSIONS: Three single nucleotide polymorphisms were associated with tissue-type plasminogen activator efficacy in the Spanish population, and their mechanism of action might be associated with the activity of coagulation factors.
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