Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts.
BACKGROUND
To investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.


METHODS
A total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.


RESULTS
We newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/microl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/microl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/microl, p = 0.004).


CONCLUSIONS
TLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.
Chen
Yung-Che
YC
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Hsiao
Chang-Chun
CC
Chen
Chung-Jen
CJ
Chin
Chien-Hung
CH
Liu
Shih-Feng
SF
Wu
Chao-Chien
CC
Eng
Hock-Liew
HL
Chao
Tung-Ying
TY
Tsen
Chia-Cheng
CC
Wang
Yi-Hsi
YH
Lin
Meng-Chih
MC
D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology*
D017931:DNA Primers; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2