title: Pharmacogenetics of the CD14 endotoxin receptor polymorphism and progression of coronary atherosclerosis.
abstract: Atherosclerosis is at least in part an inflammatory disease. CD14 is an endotoxin receptor that after binding of lipopolysaccharides evokes endothelial activation and secretion of several cytokines. A polymorphism of CD14 has been associated with myocardial infarction. We evaluated the role of the -159 T/C polymorphism in the promoter region of the CD14 gene in relation to severity and progression of coronary atherosclerosis and response to the HMG CoA reductase inhibitor pravastatin. We recruited patients from the multi-center double-blind randomized placebo controlled REGRESS trial and genotyped the -159T/C CD14 polymorphism. DNA and angiographic follow-up were available from 759 patients with objectivated coronary artery disease. We measured changes in mean segment diameter (MSD) and minimum obstruction diameter (MOD) with quantitative coronary angiography and noted the occurrence of major adverse cardiac events. The genotype distribution was 28% TT, 49% CT, 23% CC. We did not find any association between genotype and MSD and MOD at baseline, frequency of previous myocardial infarction, changes in MSD and MOD or major clinical events. Treatment with the HMG CoA reductase inhibitor pravastatin reduced progression of coronary atherosclerosis and adverse events equally for all genotypes. We conclude, that the -159T/C polymorphism in the CD14 monocyte receptor gene was not associated with progression of coronary atherosclerosis in this population nor did it influence the efficacy of pravastatin in the treatment of atherosclerosis.
authors.affiliation: Leiden University Medical Center, Department of Cardiology, C5-P, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Willem R P
authors.initials: WR
authors.lastname: Agema
authors.forename: J
authors.initials: J
authors.lastname: Wouter Jukema
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Ernst E
authors.initials: EE
authors.lastname: van der Wall
mesh_terms: D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics*; D018450:Disease Progression; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018950:Lipopolysaccharide Receptors; D011971:Receptors, Immunologic; C048071:endotoxin receptor; D017035:Pravastatin