Polymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups.
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.
Dissanayeke
Shobana Rebecca
SR
Department of Paediatric Infectious Diseases, Imperial College London, London, United Kingdom.
Levin
Samuel
S
Pienaar
Sandra
S
Wood
Kathryn
K
Eley
Brian
B
Beatty
David
D
Henderson
Howard
H
Anderson
Suzanne
S
Levin
Michael
M
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*
D017931:DNA Primers; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human
Scand J Immunol. 2007 Feb;65(2):148-57
17257219
Cytokine Growth Factor Rev. 2000 Dec;11(4):321-33
10959079
Pediatr Infect Dis J. 1998 May;17(5):407-11
9613655
N Engl J Med. 1996 Dec 26;335(26):1941-9
8960473
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71
11095740
Trends Microbiol. 2004 Apr;12(4):186-92
15051069
J Immunol. 1999 Dec 15;163(12):6748-55
10586073
J Clin Invest. 1997 Dec 1;100(11):2658-64
9389728
Nature. 2002 Nov 21;420(6913):329-33
12447442
J Interferon Cytokine Res. 2000 Oct;20(10):843-55
11054272
Semin Immunol. 2004 Feb;16(1):35-41
14751762
Nat Genet. 2008 Mar;40(3):261-2; author reply 262-3
18305471
J Infect. 2004 Jan;48(1):13-22
14667788
Immunol Cell Biol. 2007 Feb-Mar;85(2):103-11
17213830
Infect Genet Evol. 2008 Sep;8(5):541-4
18417424
J Clin Invest. 2000 May;105(10):1429-36
10811850
Electrophoresis. 2003 Jan;24(1-2):26-33
12652570
Nat Rev Genet. 2001 Dec;2(12):967-77
11733749
Am Rev Respir Dis. 1978 Apr;117(4):621-4
565607
Science. 2006 Dec 22;314(5807):1930-3
17185601
Nat Rev Genet. 2006 Feb;7(2):98-108
16418745
Nature. 2001 Sep 6;413(6851):78-83
11544529
Clin Chest Med. 2005 Jun;26(2):233-46, vi
15837108
Nat Genet. 2007 Apr;39(4):523-8
17322885
Nat Rev Genet. 2002 Apr;3(4):285-98
11967553
Mol Biol Evol. 2007 Aug;24(8):1600-3
17525472
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7871-6
10393914
Annu Rev Immunol. 1998;16:593-617
9597143
J Infect Dis. 2006 Oct 15;194(8):1127-1134
16991088
J Immunol. 1999 Oct 1;163(7):3920-7
10490993
Arch Dis Child. 1999 May;80(5):433-7
10208948