Promoter Polymorphism in the Endotoxin Receptor (CD14) Is Associated With Increased Carotid Atherosclerosis Only in Smokers

BACKGROUND AND PURPOSE: The risk of atherosclerosis from endotoxemia is increased in smokers. Endotoxin is a potent mediator of inflammation, and smokers have elevated plasma levels of endotoxin. The endotoxin receptor CD14 can enhance the endotoxin-neutralization capacity of plasma. A functional polymorphism in the promoter region of the CD14 gene (CD14 -159C/T) was studied to determine its impact on common carotid artery (CCA) intima-media thickness (IMT) and any interactions with environmental inflammatory stimuli. METHODS: A community population (n=992; aged 50 to 65 years) underwent genotypic examination for the CD14 -159 polymorphism by restriction fragment length polymorphism analysis. RESULTS: The CC genotype was associated with increased CCA IMT. The age- and sex-adjusted odds ratio for IMT above the 75th percentile was 1.63 (95% CI, 1.19 to 2.24; P=0.002) and 1.70 (95% CI, 1.18 to 2.44; P=0.004) after additional adjustment for conventional risk factors. This gene effect was found only in current smokers and ex-smokers. Multivariate analysis in this group (n=503) increased the odds ratio to 2.02 (95% CI, 1.23 to 3.34; P=0.006). No significant interactions were found in nonsmokers or with alcohol consumption. CONCLUSIONS: The CD14 -159 polymorphism is associated with increased CCA IMT in smokers from a general population. CD14 may modulate the inflammatory effects of smoking in atherogenesis.