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Gender- and age-dependent relationships between the E-selectin S128R polymorphism and coronary artery calcification
D L Ellsworth1, L F Bielak, S T Turner
1Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, National Institutes of Health, 6701 Rockledge Drive MSC 7934, Bethesda, MD 20892-7934, USA. ellsworth@nih.gov
Insights
The E-selectin S128R gene polymorphism is linked to coronary artery calcification (CAC) in younger women. This finding suggests the E-selectin 128R allele may be an early atherosclerosis risk factor in this demographic.
Area of Science:
- Cardiovascular disease research
- Genetics and molecular biology
- Immunology and inflammation
Background:
- Atherosclerosis development involves leukocyte adhesion to the vascular endothelium via cell adhesion molecules.
- A specific polymorphism in the endothelial-leukocyte adhesion molecule 1 (E-selectin) gene (S128R) is associated with severe atherosclerotic disease.
- This polymorphism affects E-selectin's ligand binding and increases cellular adhesion.
Purpose of the Study:
- To investigate the association between the E-selectin S128R polymorphism and coronary artery calcification (CAC) in asymptomatic adults.
- To determine if this genetic variation is a risk factor for atherosclerosis, particularly in younger individuals.
Main Methods:
- The study examined 294 women (40-88 years) and 314 men (30-80 years) from the Epidemiology of Coronary Artery Calcification Study.
- Coronary artery calcification (CAC) was detected using noninvasive electron beam computed tomography.
- Statistical analyses adjusted for traditional cardiovascular risk factors.
Main Results:
- No association was found between the E-selectin polymorphism and CAC in men of any age or women over 50.
- In women aged 50 or younger, the E-selectin S128R polymorphism was significantly associated with the presence of CAC.
- This association remained significant after adjusting for age, BMI, blood pressure, cholesterol levels, and smoking status.
Conclusions:
- The E-selectin 128R allele may represent a risk factor for coronary atherosclerosis in younger, asymptomatic women.
- This finding is notable as younger women often have fewer traditional risk factors and different adhesion molecule expression patterns.
- Further research is warranted to understand the role of E-selectin genetics in early atherosclerosis development in specific demographics.
Abstract:
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.