ad66763c-c3d1-4532-8f30-c7d6bb1105cc
title
Pharmacogenetics of the  CD14  endotoxin receptor polymorphism and progression of coronary atherosclerosis.
f03749d6-5c29-4f9c-809b-6a1a91b3c78a
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.