Published Online
on January 30, 2003

A more recent version of this article appeared on March 1, 2003

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Submitted on August 19, 2002
Accepted on September 17, 2002

Promoter Polymorphism in the Endotoxin Receptor (CD14) Is Associated With Increased Carotid Atherosclerosis Only in Smokers. The Carotid Atherosclerosis Progression Study (CAPS)

Paul Risley BSc^*; Paula Jerrard-Dunne MRCPI; Matthias Sitzer MD; Alexandra Buehler MD; Stefan von Kegler MD; and Hugh S. Markus FRCP

From the Department of Clinical Neurosciences, St George's Hospital Medical School, London, UK (P.R., P.J-D., H.S.M.), and Department of Neurology, Johann Wolfgang Goethe University Frankfurt am Main, Frankfurt am Main, Germany (M.S., A.B., S. von K.).

^* To whom correspondence should be addressed. E-mail: prisley{at}sghms.ac.uk.

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.

Key words: antigens, CD14 • atherosclerosis • cigarette smoking • polymorphism

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