Association of the Toll-like receptor 4 gene Asp299Gly polymorphism with acute coronary events.
OBJECTIVE
Atherosclerosis is a chronic inflammatory disease of the blood vessels. Toll-like receptor 4 (TLR4) is a transmembrane receptor that is involved in mediating inflammatory responses to bacterial endotoxin and other ligands. The aim of this study was to search for an association between a common functional polymorphism of TLR4--Asp299Gly--and acute coronary syndrome.


RESULTS
We conducted a case-control study of 183 patients with acute coronary syndromes and 216 controls. We screened the TLR4 gene for the Asp299Gly polymorphism using a 5' fluorogenic assay. The 299Gly allele was associated with a decreased risk of acute coronary events independently of standard coronary risk factors. The adjusted odds ratio associated with this allele was 0.41 (95% CI, 0.18 to 0.95; P=0.037). In controls, TLR4 heterozygosity was also associated with a significant decrease in plasma fibrinogen and soluble vascular cellular adhesion molecule-1 levels (P<0.01).


CONCLUSIONS
These results, which must be confirmed by a prospective longitudinal study, provide evidence of an association between the Asp299Gly polymorphism of the human TLR4 receptor and acute coronary syndromes. They confirm the previously reported involvement of TLR4 in carotid and femoral artery atherosclerosis.
Ameziane
Nejma
N
INSERM U479, Faculté Xavier Bichat, Paris, France.
Beillat
Tiphaine
T
Verpillat
Patrice
P
Chollet-Martin
Sylvie
S
Aumont
Marie-Claude
MC
Seknadji
Patrick
P
Lamotte
Maryse
M
Lebret
Dominique
D
Ollivier
Véronique
V
de Prost
Dominique
D
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology / Q000235:genetics*; D023921:Coronary Stenosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D018570:Risk Assessment; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D019010:Vascular Cell Adhesion Molecule-1; D001224:Aspartic Acid; D005340:Fibrinogen; D005998:Glycine