Limits...
Polymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups.

Dissanayeke SR, Levin S, Pienaar S, Wood K, Eley B, Beatty D, Henderson H, Anderson S, Levin M - PLoS ONE (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Infectious Diseases, Imperial College London, London, United Kingdom.

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.

Show MeSH

Related in: MedlinePlus

TNF induction in response to LPS in individuals with TIRAP variants.Graph shows the average TNF production in response to stimulation of whole blood with LPS from three separate experiments in Xhosa individuals with variant genotypes at positions 548 and 589 of the TIRAP gene. The error bars show the median with 95% confidence interval.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2724706&req=5

pone-0006698-g003: TNF induction in response to LPS in individuals with TIRAP variants.Graph shows the average TNF production in response to stimulation of whole blood with LPS from three separate experiments in Xhosa individuals with variant genotypes at positions 548 and 589 of the TIRAP gene. The error bars show the median with 95% confidence interval.

Mentions: In order to establish whether any of the SNPs were associated with altered TLR signalling, as has been suggested in previous studies [20], we evaluated LPS induced TNF production as a marker of inflammatory gene induction through the TLR4 pathway from all controls and cases after they had cleared the infection. Although none of the identified SNPs showed significant difference in frequency between cases and controls, significant differences were seen in TNF production for two variants. In the Xhosa group we found that individuals carrying a single copy of the novel 548G→C (R184T) or the previously identified 589G→A (V197I) SNP, showed significantly higher TNF production than those with the wildtype (p<0.05) (fig. 3).


Polymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups.

Dissanayeke SR, Levin S, Pienaar S, Wood K, Eley B, Beatty D, Henderson H, Anderson S, Levin M - PLoS ONE (2009)

TNF induction in response to LPS in individuals with TIRAP variants.Graph shows the average TNF production in response to stimulation of whole blood with LPS from three separate experiments in Xhosa individuals with variant genotypes at positions 548 and 589 of the TIRAP gene. The error bars show the median with 95% confidence interval.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2724706&req=5

pone-0006698-g003: TNF induction in response to LPS in individuals with TIRAP variants.Graph shows the average TNF production in response to stimulation of whole blood with LPS from three separate experiments in Xhosa individuals with variant genotypes at positions 548 and 589 of the TIRAP gene. The error bars show the median with 95% confidence interval.
Mentions: In order to establish whether any of the SNPs were associated with altered TLR signalling, as has been suggested in previous studies [20], we evaluated LPS induced TNF production as a marker of inflammatory gene induction through the TLR4 pathway from all controls and cases after they had cleared the infection. Although none of the identified SNPs showed significant difference in frequency between cases and controls, significant differences were seen in TNF production for two variants. In the Xhosa group we found that individuals carrying a single copy of the novel 548G→C (R184T) or the previously identified 589G→A (V197I) SNP, showed significantly higher TNF production than those with the wildtype (p<0.05) (fig. 3).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatric Infectious Diseases, Imperial College London, London, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus