The Asp²⁹⁹Gly Toll-like receptor 4 polymorphism in advanced aortic atherosclerosis

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Abstract

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 <i>vs</i> 15.5%, p=0.83). Moreover, ²⁹⁹Gly carriership was not associated with
the extensiveness of (advanced) aortic atherosclerosis
(p=0.64).
Conclusion: Our results suggest that the Asp²⁹⁹Gly TLR-4 receptor polymorphism is not associated with the prevalence nor extensiveness of (advanced) aortic atherosclerosis.