title: Toll-like receptor polymorphisms are associated with increased neurosyphilis risk.
abstract: BACKGROUND
  Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) 1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. We investigated whether common SNPs in TLR1, TLR2, or TLR6 were associated with laboratory- or clinically-defined neurosyphilis.
  
  
  METHODS
  Polymorphisms in the genes for TLR1 (a T→G mutation at position 1805), TLR2 (a G→A mutation at position 2258), and TLR6 (a C→T mutation at position 745) were sought in 456 white patients with syphilis. Laboratory-defined neurosyphilis included a reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test. Clinically-defined neurosyphilis included new vision or hearing loss. Controls had CSF white blood cells of 5/μL or less, nonreactive CSF-Venereal Disease Research Laboratory, and no vision or hearing loss.
  
  
  RESULTS
  Overall, 26.2% of patients had laboratory-defined and 36.2% had clinically-defined neurosyphilis. Compared with controls, patients with any of the 3 SNPs were more likely to have laboratory-defined neurosyphilis. Those with TLR2 or TLR6 SNPs were more likely to have clinically-defined neurosyphilis. These associations were independent of serum rapid plasma reagin titer.
  
  
  CONCLUSIONS
  A common TLR1 polymorphism is associated with an increased risk of laboratory-defined neurosyphilis, and common TLR2 and TLR6 polymorphisms are associated with an increased risk of both laboratory- and clinically-defined neurosyphilis. These data suggest that host factors impact the natural history of syphilis.
authors.affiliation: From the *Departments of Neurology and †Medicine, University of Washington, Seattle, WA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Sahi
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Tantalo
authors.forename: Emily L
authors.initials: EL
authors.lastname: Ho
authors.forename: Shelia B
authors.initials: SB
authors.lastname: Dunaway
authors.forename: Trudy
authors.initials: T
authors.lastname: Jones
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hawn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009494:Neurosyphilis / Q000134:cerebrospinal fluid / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013129:Spinal Puncture / Q000379:methods*; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D014210:Treponema pallidum / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D015415:Biomarkers; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6