Gender- and age-dependent relationships between the E-selectin S128R polymorphism and coronary artery calcification

Development and progression of atherosclerosis involves recruitment and binding of circulating leukocytes to areas of inflammation within the vascular endothelium mediated by a diverse array of cellular adhesion molecules. A polymorphism in the endothelial-leukocyte adhesion molecule 1 (E-selectin) gene has been implicated in early-onset, angiographically defined, severe atherosclerotic disease because it profoundly affects ligand recognition and binding specificity, resulting in a significant increase in cellular adhesion. Relationships between the E-selectin S128R polymorphism and coronary artery calcification (CAC), a marker of atherosclerosis detected with noninvasive electron beam computed tomography, were examined in 294 asymptomatic women aged 40--88 years and 314 asymptomatic men aged 30--80 years from the Epidemiology of Coronary Artery Calcification Study. The E-selectin polymorphism was not associated with presence of CAC in men of any age or in women over age 50. In women 50 years of age or younger the E-selectin polymorphism was significantly associated with presence of CAC after adjustment for age, body mass index, systolic blood pressure, ratio of total cholesterol to high-density lipoprotein cholesterol, and smoking. The significant association between E-selectin and CAC in women 50 years of age or younger may suggest that the 128R allele is a risk factor for coronary atherosclerosis in younger asymptomatic women, who typically have lower levels of traditional risk factors and reduced adhesion molecule expression due to the presence of higher levels of endogenous hormones.