Functional polymorphisms in toll-like receptor 4 are associated with worse outcome in acute ischemic stroke patients.
Toll-like receptor-4 (TLR4) is important in neuroinflammation. Single nucleotide polymorphisms (SNPs) in TLR4, including 1063 A/G [Asp299Gly] and 1363 C/T [Thr399Ile], are associated with altered immune responses but their effect on acute ischemic stroke (AIS) outcome is unknown. We collected demographic, clinical, laboratory, radiologic, and genotype data on 113 AIS patients and performed multivariate analyses to assess associations between TLR4 SNP haplotype and either neurological outcome, infection, or inflammatory markers. In adjusted analyses, TLR4 SNPs were associated with worse outcome as well as increases in circulating leukocytes, C-reactive protein, and interleukin-1 receptor antagonist. In AIS, variations in TLR4 may influence neurological outcome (for video abstract, please see Supplemental digital content 1 file, http://links.lww.com/WNR/A274).
Departments of aNeurology bRadiology cBiostatistics, University of Washington, Seattle, Washington, USA.
Jonathan R
JR
Weinstein
Juliane
J
Schulze
Richard V
RV
Lee
Hunter
H
Phillips
Dannielle
D
Zierath
Patricia
P
Tanzi
Dean
D
Shibata
Kevin C
KC
Cain
Kyra J
KJ
Becker
D000368:Aged; D016207:Cytokines / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000097:blood / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D016207:Cytokines; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4