Issue: 2007 > June > original article

The Asp<sup>299</sup>Gly Toll-like receptor 4 polymorphism in advanced aortic atherosclerosis

M.J. Hommels, A.A. Kroon, M.G. Netea, P.W. de Leeuw, C.A. Bruggeman, T. Leiner, D.A. Koster, A.F.H. Stalenhoef, A.J.A.M. van der Ven


Background: Recently, the common Asp<sup>299</sup>Gly 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 Asp<sup>299</sup>Gly
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 (Asp<sup>299</sup>Gly) 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
<sup>299</sup>Gly allele, whereas none of the subjects were <sup>299</sup>Gly homozygous (<sup>299</sup>Gly allele frequency 7.8%). The prevalence of the <sup>299</sup>Gly 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, <sup>299</sup>Gly carriership was not associated with
the extensiveness of (advanced) aortic atherosclerosis
Conclusion: Our results suggest that the Asp<sup>299</sup>Gly TLR-4 receptor polymorphism is not associated with the prevalence nor extensiveness of (advanced) aortic atherosclerosis.