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

Sequence variation in TIRAP in the Mixed ancestry and Xhosa cases and controls.Representation of the opening reading frame of the TIRAP gene with the frequency of SNPs in the A) Mixed ancestry group and in the B) Xhosa group at various positions in the gene. Red blocks represent the coding region and the yellow blocks the 3′ UTR. Bold numbers and letters show published SNPs. Heterozygous SNPs with position in the gene are shown above the gene diagram; homozygous SNPs with base change and amino acid change (if nonsynonymous) shown below the gene diagram.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2724706&req=5

pone-0006698-g001: Sequence variation in TIRAP in the Mixed ancestry and Xhosa cases and controls.Representation of the opening reading frame of the TIRAP gene with the frequency of SNPs in the A) Mixed ancestry group and in the B) Xhosa group at various positions in the gene. Red blocks represent the coding region and the yellow blocks the 3′ UTR. Bold numbers and letters show published SNPs. Heterozygous SNPs with position in the gene are shown above the gene diagram; homozygous SNPs with base change and amino acid change (if nonsynonymous) shown below the gene diagram.

Mentions: Having identified SNPs in the coding region in each ethnic group, we next sought to identify any association between individual TIRAP variants, or combinations of variants, with disease. Table 2 shows the frequency in cases and controls of each of the identified SNPS, and figure 1 displays the pattern of variation across the gene for both heterozygous and homozygous individuals. There were no statistically significant differences between the frequency of any individual SNP between cases and controls in either cohort.


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)

Sequence variation in TIRAP in the Mixed ancestry and Xhosa cases and controls.Representation of the opening reading frame of the TIRAP gene with the frequency of SNPs in the A) Mixed ancestry group and in the B) Xhosa group at various positions in the gene. Red blocks represent the coding region and the yellow blocks the 3′ UTR. Bold numbers and letters show published SNPs. Heterozygous SNPs with position in the gene are shown above the gene diagram; homozygous SNPs with base change and amino acid change (if nonsynonymous) shown below the gene diagram.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006698-g001: Sequence variation in TIRAP in the Mixed ancestry and Xhosa cases and controls.Representation of the opening reading frame of the TIRAP gene with the frequency of SNPs in the A) Mixed ancestry group and in the B) Xhosa group at various positions in the gene. Red blocks represent the coding region and the yellow blocks the 3′ UTR. Bold numbers and letters show published SNPs. Heterozygous SNPs with position in the gene are shown above the gene diagram; homozygous SNPs with base change and amino acid change (if nonsynonymous) shown below the gene diagram.
Mentions: Having identified SNPs in the coding region in each ethnic group, we next sought to identify any association between individual TIRAP variants, or combinations of variants, with disease. Table 2 shows the frequency in cases and controls of each of the identified SNPS, and figure 1 displays the pattern of variation across the gene for both heterozygous and homozygous individuals. There were no statistically significant differences between the frequency of any individual SNP between cases and controls in either cohort.

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