title: Polymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups.
abstract: Host recognition of mycobacterial surface molecules occurs through toll like receptors (TLR) 2 and 6. The adaptor protein TIRAP mediates down stream signalling of TLR2 and 4, and polymorphisms in the TIRAP gene (TIRAP) have been associated with susceptibility and resistance to tuberculosis (TB) in adults. In order to investigate the role of polymorphic variation in TIRAP in childhood TB in South Africa, which has one of the highest TB incidence rates in the world, we screened the entire open reading frame of TIRAP for sequence variation in two cohorts of childhood TB from different ethnic groups (Xhosa and mixed ancestry). We identified 13 SNPs, including seven previously unreported, in the two cohorts, and found significant differences in frequency of the variants between the two ethnic groups. No differences in frequency between individual SNPs or combinations were found between TB cases and controls in either cohort. However the 558C-->T SNP previously associated with TB meningitis (TBM) in a Vietnamese population was found to be associated with TBM in the mixed ancestry group. Polymorphisms in TIRAP do not appear to be involved in childhood TB susceptibility in South Africa, but may play a role in determining occurrence of TBM.
authors.affiliation: Department of Paediatric Infectious Diseases, Imperial College London, London, United Kingdom.
authors.forename: Shobana Rebecca
authors.initials: SR
authors.lastname: Dissanayeke
authors.forename: Samuel
authors.initials: S
authors.lastname: Levin
authors.forename: Sandra
authors.initials: S
authors.lastname: Pienaar
authors.forename: Kathryn
authors.initials: K
authors.lastname: Wood
authors.forename: Brian
authors.initials: B
authors.lastname: Eley
authors.forename: David
authors.initials: D
authors.lastname: Beatty
authors.forename: Howard
authors.initials: H
authors.lastname: Henderson
authors.forename: Suzanne
authors.initials: S
authors.lastname: Anderson
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D017931:DNA Primers; D005006:Ethnicity; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008562:Membrane Glycoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*
chemical_list: D017931:DNA Primers; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human
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