title: Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms.
abstract: BACKGROUND
  Toll-like receptors (TLRs) are involved in the recognition of conserved microbial structures, leading to activation of an inflammatory response and formation of an adaptive immune response.
  
  
  METHODS
  Twenty-three polymorphisms in five TLR genes were genotyped in 729 tuberculosis cases and 487 healthy controls in a population-based case-control association study in a South African population.
  
  
  RESULTS
  We detected sex-specific associations for TLR8 polymorphisms, with rs3761624 (OR=1.54, p<0.001), rs3764879 (OR=1.41, p=0.011) and rs3764880 (OR=1.42, p=0.011) associated in females and rs3764879 (OR=0.72, p=0.013) and rs3764880 (OR=0.75, p=0.036) associated in males. Epistatic interactions between the TLR genes were investigated and the TLR1_rs4833095 polymorphism was shown to interact with TLR2_rs3804100 and (GT)n microsatellite (p=0.002) and alter susceptibility to TB. We also studied the role of TLRs in disease caused by different Mycobacterium tuberculosis genotypes in 257 tuberculosis cases, and identified associations between specific TLR polymorphisms and disease caused by specific strains.
  
  
  CONCLUSIONS
  This study provides further evidence that the TLRs play an important role in the outcome of tuberculosis disease, and suggests a partial explanation for the male bias in tuberculosis ratios.
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa.
authors.forename: Muneeb
authors.initials: M
authors.lastname: Salie
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa.
authors.forename: Michelle
authors.initials: M
authors.lastname: Daya
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa.
authors.forename: Lance A
authors.initials: LA
authors.lastname: Lucas
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Warren
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa.
authors.forename: Gian D
authors.initials: GD
authors.lastname: van der Spuy
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa.
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa.
authors.forename: Eileen G
authors.initials: EG
authors.lastname: Hoal
authors.affiliation: MRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg 7505, South Africa. Electronic address: marlom@sun.ac.za.
authors.forename: Marlo
authors.initials: M
authors.lastname: Möller
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012727:Sex Characteristics; D051200:Toll-Like Receptor 8 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics*; D055815:Young Adult
chemical_list: C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8
keywords: Host–pathogen; Mycobacterium tuberculosis; Polymorphism; Susceptibility; Toll-like receptors; Tuberculosis