Document Detail


Promoter polymorphism in the endotoxin receptor (CD14) is associated with increased carotid atherosclerosis only in smokers: the Carotid Atherosclerosis Progression Study (CAPS).
MedLine Citation:
PMID:  12624278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Paul Risley; Paula Jerrard-Dunne; Matthias Sitzer; Alexandra Buehler; Stefan von Kegler; Hugh S Markus;
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-01-30
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  34     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-07     Completed Date:  2003-03-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  600-4     Citation Subset:  IM    
Affiliation:
Department of Clinical Neurosciences, St George's Hospital Medical School, Cranmer Terr, Tooting, London SW17 0RE, UK. prisley@sghms.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Aged
Alcohol Drinking / epidemiology
Alleles
Antigens, CD14 / genetics*
Carotid Arteries / ultrasonography
Carotid Artery Diseases / epidemiology,  genetics*,  ultrasonography
Comorbidity
Disease Progression
Female
Genetic Predisposition to Disease
Genetic Testing
Germany / epidemiology
Humans
Male
Middle Aged
Multivariate Analysis
Odds Ratio
Polymorphism, Genetic*
Polymorphism, Restriction Fragment Length
Receptors, Immunologic / genetics*
Risk Assessment
Risk Factors
Smoking* / epidemiology
Tunica Intima / ultrasonography
Tunica Media / ultrasonography
Chemical
Reg. No./Substance:
0/Antigens, CD14; 0/Receptors, Immunologic; 0/endotoxin receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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