Published Online
on January 16, 2003

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

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Submitted on September 4, 2002
Accepted on September 11, 2002

Interleukin-6 Promoter Polymorphism Modulates the Effects of Heavy Alcohol Consumption on Early Carotid Artery Atherosclerosis. The Carotid Atherosclerosis Progression Study (CAPS)

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

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

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

Background and Purpose--A J-shaped relationship has been demonstrated between alcohol and both clinical cardiovascular events and carotid atherosclerosis. A similar J-shaped relationship has been found between alcohol intake and inflammatory markers. If inflammation were on the intermediate causal pathway between alcohol intake and atherosclerosis, then genetic determinants of enhanced inflammation would be expected to modify this relationship.

Methods--In a large community population (n=1000; age, 50 to 65 years), we studied the effects of the interleukin-6 (IL-6)-174 polymorphism and gene-alcohol interactions on common carotid artery intima-media thickness (CCA-IMT) and carotid plaque.

Results--The CC genotype was associated with significantly higher IL-6 levels; the odds ratio (OR) for IL-6 in the top quartile was 2.07 (95% CI, 1.16 to 3.72; P=0.014). Interactions were seen between genotype and alcohol consumption for both IL-6 levels and CCA-IMT. In individuals who drank >30 g/d of alcohol, the CC genotype was associated with higher IL-6 levels, elevated CCA-IMT (P=0.001), and increased risk of carotid plaque (OR, 3.64; 95% CI, 1.15 to 11.54; P=0.028). The J-shaped relationship between alcohol intake and IMT was seen only for the CC genotype.

Conclusions--These data suggest that the IL-6-174 promotor polymorphism may modulate the effects of alcohol on carotid atherosclerosis. These data support the hypothesis that inflammation forms part of the intermediate causal pathway between alcohol intake and atherosclerosis.

Key words: alcohol • atherosclerosis • genes • inflammation • interleukins

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