Toll-like receptor 4 polymorphism is associated with coronary stenosis but not with the occurrence of acute or old myocardial infarctions.
OBJECTIVE
Atherosclerosis is considered to be a chronic inflammatory disease. Toll-like receptor 4 (TLR-4), a key mediator in activating inflammatory cascade, has an A-to-G functional polymorphism that changes aspartic acid to glycine at position 299. TLR-4 is activated by, for example, lipopolysaccharides. The purpose of this study was to investigate the role of a common Asp299Gly polymorphism of the TLR-4 gene in atherosclerosis.


METHODS
The study comprised autopsy material from 657 men (the Helsinki Sudden Death Study; mean age 53, range 33-70 years).


RESULTS
Fewer G-allele carriers had 3-vessel coronary artery disease compared with AA homozygotes (OR 0.32; 95 % CI, 0.12-0.88, p = 0.027), and they also had a lower mean value for maximal coronary stenosis (p = 0.019). TLR-4 polymorphism was not significantly associated with the occurrence of acute or old myocardial infarction (MI).


CONCLUSIONS
The G allele of the TLR-4 gene, which is associated with a lower inflammation response, was associated with a lower risk of coronary stenosis but not with the occurrence of MI and hence is not a major factor in the development of coronary atherosclerosis.
Hernesniemi
J
J
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital and the Medical School at the University of Tampere, Finland. jussi.hernesniemi@uta.fi
Lehtimäki
T
T
Rontu
R
R
Islam
M S
MS
Eklund
C
C
Mikkelsson
J
J
Ilveskoski
E
E
Kajander
O
O
Goebeler
S
S
Viiri
L E
LE
Hurme
M
M
Karhunen
P J
PJ
D000208:Acute Disease; D015897:Comorbidity; D023921:Coronary Stenosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D044465:White People / Q000235:genetics
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4