title: Common polymorphisms in TLR4 gene associated with susceptibility to pulmonary tuberculosis in the Sudanese.
abstract: METHODS
  Host genetic risk factors influence susceptibility to tuberculosis (TB). There is ample evidence supporting the involvement of toll-like receptor 4 (TLR4) in mycobacterial infection.
  
  
  OBJECTIVE
  To study the relationship between the TLR4 gene and TB susceptibility  in the Sudanese population.
  
  
  METHODS
  A case-control study was conducted among 207 patients with pulmonary TB and 395 healthy controls. Ten tag single nucleotide polymorphisms (SNPs) of the TLR4 gene were genotyped using restriction digestion or hybridisation assays, and analysed.
  
  
  RESULTS
  The genotypes were in Hardy-Weinberg equilibrium. After controlling for sex using the Mantel-Haenszel test, four SNPs showed significant differences between cases and controls, even after correction of multiple comparisons by Bonferroni procedure. The Mantel-Haenszel estimates of allelic odds  ratios for the high-risk alleles were 1.67 for rs1927911 (P = 0.0001), 1.85 for rs5030725 (P = 0.0008), 2.14 for rs7869402 (P = 1.87e-07) and 2.31 for rs1927906 (P = 1.23e-10). Haplotype analysis showed that rs1927911 and rs5030725 were in one haplotype block, and  rs7869402 and rs1927906 were in another haplotype block. Conditional haplotype analysis suggested the presence of one causal variant downstream of a recombination hot spot at the 3' region of the TLR4 gene.
  
  
  CONCLUSIONS
  This is the first study to show that common TLR4  polymorphisms are associated with TB susceptibility in the Sudanese population.
authors.affiliation: Department of Molecular Biology, National Cancer Institute, University of Gezira, Wad Medani, Sudan.
authors.forename: H Y
authors.initials: HY
authors.lastname: Zaki
authors.forename: K H
authors.initials: KH
authors.lastname: Leung
authors.forename: W C
authors.initials: WC
authors.lastname: Yiu
authors.forename: N
authors.initials: N
authors.lastname: Gasmelseed
authors.forename: N E M
authors.initials: NE
authors.lastname: Elwali
authors.forename: S P
authors.initials: SP
authors.lastname: Yip
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009164:Mycobacterium Infections / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013397:Sudan; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4