http://stroke.ahajournals.org/content/43/10/2659.abstract
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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