title: Poststroke fatigue: hints to a biological mechanism.
abstract: BACKGROUND
  Poststroke fatigue (PSF) is common, but the biological basis of this fatigue is unknown. We explored the possibility that PSF is related to systemic inflammation by investigating polymorphisms in 2 genes that affect the immune response.
  
  
  METHODS
  In a substudy of a larger trial that evaluated the role of the immune response on stroke outcome, fatigue was assessed at 30, 90, 180, and 365 days after ischemic stroke using the Fatigue Assessment Scale. Subjects were genotyped for 3 single nucleotide polymorphisms, one in the interleukin-1 receptor antagonist gene (IL1RN; rs4251961, a T/C substitution) and two in the in toll-like receptor-4 (TLR4) gene (1063 A/G [Asp299Gly] rs4986790 and 1363 C/T [Thr399Ile] rs4986791).
  
  
  RESULTS
  Of the 39 participants, 22 (56%) endorsed fatigue during the study. The degree of fatigue was remarkably constant over time and independent of stroke outcome. The C allele of the rs4251961 single nucleotide polymorphism (SNP) in IL1RN was associated with self-reported fatigue (P = .03), whereas the cosegregating polymorphisms in TLR4 were associated with lower levels of fatigue (P= .04).
  
  
  CONCLUSIONS
  SNPs in 2 genes with opposing effects on inflammatory immune responses were significantly, but differentially, associated with PSF. These findings suggest a direct link between immune signaling dysregulation and PSF.
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, Washington. Electronic address: kjb@uw.edu.
authors.forename: Kyra
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Psychiatry, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Ruth
authors.initials: R
authors.lastname: Kohen
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Richard
authors.initials: R
authors.lastname: Lee
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Patricia
authors.initials: P
authors.lastname: Tanzi
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Dannielle
authors.initials: D
authors.lastname: Zierath
authors.affiliation: Department of Biostatistics, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cain
authors.affiliation: Biobehavioral Nursing and Health Systems, University of Washington School of Nursing, Seattle, Washington.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weinstein
mesh_terms: D000328:Adult; D000368:Aged; D005221:Fatigue / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: IL1RN; Poststroke fatigue; TLR4; inflammation; polymorphisms