Premium
Toll‐like receptor‐4 Asp299Gly polymorphism does not influence progression of atherosclerosis in patients with familial hypercholesterolaemia
Author(s) -
Netea M. G.,
Hijmans A.,
Van Wissen S.,
Smilde T. J.,
Trip M. D.,
Kullberg B. J.,
De Boo T.,
Van der Meer J. W. M.,
Kastelein J. J. P.,
Stalenhorf A. F. H.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01303.x
Subject(s) - allele , reductase , medicine , hmg coa reductase , tlr4 , pathogenesis , endocrinology , allele frequency , polymorphism (computer science) , receptor , gastroenterology , immunology , biology , gene , genetics , enzyme , biochemistry
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.