Toll‐like receptor‐4 Asp299Gly polymorphism does not influence progression of atherosclerosis in patients with familial hypercholesterolaemia

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Abstract
Background Toll-like receptor-4 (TLR4) is a major receptor for inflammatory stimuli potentially involved in the pathogenesis of atherosclerosis, such as lipopolysaccharide (LPS) and heat-shock proteins. The Asp299Gly polymorphism of the TLR4 gene has been associated with a reduced intima-media thickness (IMT) of the common carotid artery in healthy individuals. We have investigated whether the presence of the Asp299Gly polymorphism in patients with familial hypercholesterolaemia (FH) has a similar protective effect, and whether it influences the effects of HMG-CoA reductase treatment. Materials and methods A cohort of 293 FH patients and 200 healthy volunteers were genotyped for the presence of the Asp299Gly allele using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Intima-media thickness measurements, inflammatory parameters and the effect of HMG-CoA reductase inhibitors were compared between the patients with and without Asp299Gly allele. Results The Asp299Gly allele was present in 10·6% of the FH patients and 11·0% of the healthy individuals. Whereas the FH patients carrying the Asp299Gly allele displayed a reduced absolute IMT value compared with the FH patients carrying the wild-type allelle, the difference did not reach statistical significance. In addition, the effect of treatment with HMG-CoA reductase inhibitors was not influenced by the presence of Asp299Gly allele. Conclusion The presence of the Asp299Gly allele of the TLR4 gene does not seem to exert a major influence on the progression of atherosclerosis in patients with FH.