A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences.
The human Toll-like receptor 2 (TLR2) mediates responses of both innate and adaptive immunity to Gram-positive bacteria, including mycobacteria. We sought functional polymorphisms in the 5'-untranslated region (UTR) of TLR2. We found a highly polymorphic (GT)n dinucleotide repeat 100 bp upstream of the TLR2 translational start site in intron 2. The numbers of GT repeats varied from 12 to 28. There were significant differences in allele distribution between African Americans and Caucasians (P=0.008) and between African Americans and Koreans (P=0.0003). The promoter activities of recombinant promoter-intron2/reporter constructs including the shortest [GT)n=12] or longest [(GT)n=28] alleles were significantly more stimulated when exposed to 200 IU ml(-1) of interferon-gamma than when exposed to 100 IU ml(-1) of GM-CSF (P<==0.03). Since TLR2 plays a critical role in the human innate immune response, this functional microsatellite polymorphism may be important in the pathogenesis of infectious and inflammatory diseases.
Yim
Jae-Joon
JJ
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, Seoul, South Korea.
Ding
Li
L
Schäffer
Alejandro A
AA
Park
Gye Young
GY
Shim
Young-Soo
YS
Holland
Steven M
SM
D000483:Alleles; D006801:Humans; D007438:Introns / Q000235:genetics* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D018895:Microsatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044469:Racial Groups; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors