The Asp299Gly Toll-like receptor 4 polymorphism in advanced aortic atherosclerosis.
BACKGROUND
Recently, the common Asp299Gly polymorphism of the Toll-like receptor 4 (TLR-4) was found to be associated with a reduced incidence of acute myocardial infarction and carotid atherosclerosis. As TLR-4 signalling is causally involved in atherogenesis, the polymorphism was postulated to impart protection from atherosclerosis. To explore a potential atheroprotective effect, we studied the association between the Asp299Gly polymorphism and atherosclerosis in hypertensive patients undergoing angiography for suspected renovascular disease.


METHODS
140 hypertensive subjects underwent intraarterial digital subtraction angiography, during which the presence of atherosclerotic lesions was assessed at the level of the abdominal aorta and renal arteries. Extensiveness of disease was classified as follows: atherosclerosis confined to the abdominal aorta, unilateral renal artery stenosis or bilateral renal artery stenosis. Subsequently, genotyping for the +896 A>G (Asp299Gly) single nucleotide polymorphism was performed in all patients. In statistical analyses 17 patients were excluded because of incomplete data (n=3) or a diagnosis of fibromuscular disease (n=14).


RESULTS
21 patients were found heterozygous for the 299Gly allele, whereas none of the subjects were 299Gly homozygous (299Gly allele frequency 7.8%). The prevalence of the 299Gly allele in atherosclerotic patients was not different from the prevalence observed in subjects without atherosclerotic lesions (16.9 vs 15.5%, p=0.83). Moreover, 299Gly carriership was not associated with the extensiveness of (advanced) aortic atherosclerosis (p=0.64).


CONCLUSIONS
Our results suggest that the Asp299Gly TLR-4 receptor polymorphism is not associated with the prevalence nor extensiveness of (advanced) aortic atherosclerosis.
Hommels
M J
MJ
Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM) and Maastricht University Hospital, Maastricht, the Netherlands. M.Hommels@INTMED.unimaas.nl
Kroon
A A
AA
Netea
M G
MG
de Leeuw
P W
PW
Bruggeman
C A
CA
Leiner
T
T
Koster
D A
DA
Stalenhoef
A F H
AF
van der Ven
A J A M
AJ
D000208:Acute Disease; D019943:Amino Acid Substitution; D015901:Angiography, Digital Subtraction; D001012:Aorta, Abdominal / Q000473:pathology*; D001018:Aortic Diseases / Q000235:genetics* / Q000503:physiopathology; D001161:Arteriosclerosis / Q000235:genetics* / Q000503:physiopathology; D017023:Coronary Angiography; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D012306:Risk; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4