title: Toll-like receptor-4 Asp299Gly polymorphism does not influence progression of atherosclerosis in patients with familial hypercholesterolaemia.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Medical Center, St. Radboud, Nijmegen, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: A
authors.initials: A
authors.lastname: Hijmans
authors.forename: S
authors.initials: S
authors.lastname: van Wissen
authors.forename: T J
authors.initials: TJ
authors.lastname: Smilde
authors.forename: M D
authors.initials: MD
authors.lastname: Trip
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: T
authors.initials: T
authors.lastname: de Boo
authors.forename: J W M
authors.initials: JW
authors.lastname: Van der Meer
authors.forename: J J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: A F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: A F H
authors.initials: AF
authors.lastname: Stalenhorf
mesh_terms: D000328:Adult; D000368:Aged; D002340:Carotid Artery Diseases / Q000209:etiology / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors