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.