title: Toll-like receptor 2 subfamily gene polymorphisms are associated with Bacillus Calmette-Guérin osteitis following newborn vaccination.
abstract: OBJECTIVE
  Toll-like receptor (TLR) 1, 2, 6 and 10, the TLR2 subfamily, are known to be associated with immunity against tuberculosis. We evaluated whether polymorphisms in genes encoding TLR1, TLR2 and TLR6 were associated with osteitis in infants who received the Bacillus Calmette-Guérin (BCG) vaccination soon after birth.
  
  
  METHODS
  Blood samples from 132 adults aged 21-49 who had BCG osteitis in early childhood were analysed in a controlled study for TLR1 T1805G (rs5743618), TLR2 G2258A (rs5743708) and TLR6 C745T (rs5743810) gene single nucleotide polymorphisms.
  
  
  RESULTS
  The frequencies of the variant genotypes differed between the cases and controls: 11.4% versus 5.7% for TLR2 G2258A (p = 0.033) and 77.3% versus 61.6% for TLR6 C745T (p = 0.001). The TLR2 and TLR6 variant genotypes were associated with a higher risk of BCG osteitis, with adjusted odds ratios (aOR) of 2.154 (95%CI 1.026-4.521) and 1.907 (95%CI 1.183-3.075), respectively. The frequency of the TLR1 T1805G variant genotype was 19.7% in the cases and 33.6% in the controls (p = 0.003). The TLR1 variant genotype was associated with a lower risk of BCG osteitis (aOR 0.554, 95%CI 0.336-0.911).
  
  
  CONCLUSIONS
  Gene polymorphisms that regulate the function of the TLR2 subfamily play a role in the development of BCG osteitis in vaccinated infants.
authors.affiliation: Center for Child Health Research, University of Tampere and University Hospital, Tampere, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Pöyhönen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Nuolivirta
authors.forename: Juho
authors.initials: J
authors.lastname: Vuononvirta
authors.forename: Liisa
authors.initials: L
authors.lastname: Kröger
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Jussi
authors.initials: J
authors.lastname: Mertsola
authors.forename: Qiushui
authors.initials: Q
authors.lastname: He
authors.forename: Matti
authors.initials: M
authors.lastname: Korppi
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010000:Osteitis / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6
keywords: Bacillus Calmette-Guérin; Osteitis; Toll-like receptor 1; Toll-like receptor 2; Toll-like receptor 6