Intercellular adhesion molecule 1 (ICAM-1) gene variant is associated with coronary artery calcification independent of soluble ICAM-1 levels.
BACKGROUND
Although circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) predict cardiovascular events, no studies have examined intercellular adhesion molecule 1 (ICAM-1) gene variants, plasma sICAM-1 levels, and atherosclerosis in the same sample.


METHODS
We examined the association of the ICAM-1 K469E gene variant and plasma sICAM-1 with coronary artery calcification (CAC) in 632 asymptomatic subjects, recruited on the basis of a family history of premature cardiovascular disease.


RESULTS
In age-adjusted ordinal regression, sICAM-1 levels were associated with CAC (odds ratio [OR] [95% confidence interval (CI)] 1.30 [1.04-1.6] per 100 ng/dL sICAM-1; p = .02), but this association was lost after adjusting for traditional risk factors (OR [95% CI] 0.9 [0.69-1.16]). In men, but not women (interaction p = .018), the ICAM-1 K469E GG genotype predicted lower CAC after adjusting for traditional risk factors (OR [95% CI] 0.33 [0.17-0.61]; p = .001) and further controlling for plasma sICAM-1 (OR [95% CI] 0.27 [0.14-0.52]; p < .001).


CONCLUSIONS
In a study sample specifically selected for the characteristic of a family history of premature coronary heart disease, ICAM K469E GG was associated with lower CAC scores in men but not women even after controlling for plasma levels of sICAM-1. These studies suggest that ICAM-1 variants may modulate atherosclerosis in humans and provide support for the concept that inflammatory gene polymorphisms may influence atherosclerosis independent of plasma levels of their gene products.
Reilly
Muredach P
MP
Cardiovascular Division, Department of Medicine, the Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. muredach@spirit.gcrc.upenn.edu
Wolfe
Megan L
ML
Dykhouse
Jennifer
J
Reddy
Karthik
K
Localio
A Russell
AR
Rader
Daniel J
DJ
D000328:Adult; D000483:Alleles; D002114:Calcinosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged
D018799:Intercellular Adhesion Molecule-1