Toll-like receptor (TLR)-9 promotor polymorphisms and atherosclerosis.
BACKGROUND
Currently, the primary cause of atherosclerosis remains controversial: while oxidized or enzymatically altered LDL is widely accepted as one cause of the inflamed lesion, microorganisms such as C. pneumoniae or cytomegalovirus (CMV) also have recently been postulated to be involved in the pathogenesis of atherosclerosis. Microbial products activate innate immune cells of the host via Toll-like receptors (TLRs). Common polymorphisms of the TLR-2 and TLR-4 genes have been shown to be associated with an increased risk for restenosis after PTCA, and a lower risk of carotid atherosclerosis, respectively. Microbial DNA has been shown to activate immune cells via the cytosolic TLR-9. Specially, C. pneumonia and CMV as intracellular pathogens may be potent trigger of TLR-9 signaling. Therefore, we investigated whether the two common promotor polymorphisms of the TLR-9 gene are correlated with atherogenesis.


METHODS
The T-1237C and the T-1486C polymorphisms were analyzed by Real Time PCR in 202 (derivation study, age 58.1, SD 10.0) and 182 (validation study, age 59.7, SD 9.6) patients that underwent angioplasty and 188 healthy controls (age 52.5, SD 6.1). Restenosis was defined as >50% luminal diameter reduction at follow-up angiography.


RESULTS
We found the two polymorphism being able to create new potential binding sites for transcription factors, however, no association of the TLR-9 polymorphisms with atherogenesis or restenosis was detectable.


CONCLUSIONS
Our data indicate that the two TLR-9 promotor polymorphisms are not involved in atherogenesis.
Hamann
Lutz
L
Institute for Microbiology and Hygiene, Charité University Medical Center, Medicine, Dorotheenstrasse 96, 10117 Berlin, Germany. lutz.hamann@charite.de
Glaeser
Christiane
C
Hamprecht
Axel
A
Gross
Michael
M
Gomma
Abuzeid
A
Schumann
Ralf R
RR
D000368:Aged; D000483:Alleles; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
D051217:Toll-Like Receptor 9