Interleukin-6 promoter polymorphism modulates the effects of heavy alcohol consumption on early carotid artery atherosclerosis: the Carotid Atherosclerosis Progression Study (CAPS).
OBJECTIVE
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.
Jerrard-Dunne
Paula
P
Department of Clinical Neurosciences, St. Georges Hospital Medical School, Tooting, London, UK. pjerrard@sghms.ac.uk
Sitzer
Matthias
M
Risley
Paul
P
Steckel
Donata A
DA
Buehler
Alexandra
A
von Kegler
Stefan
S
Markus
Hugh S
HS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015897:Comorbidity; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D015850:Interleukin-6