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Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery
S C Barbaux1, S Blankenberg, H J Rupprecht
1Institut National de la Santé et de la Recherche Médicale (INSERM) U525, Paris, France.
Insights
Soluble P-selectin levels are linked to coronary artery disease (CAD) risk, influenced by gene variations. This study found a complex, age-dependent relationship between P-selectin and CAD, suggesting varied roles in the disease process.
Area of Science:
- Cardiovascular biology
- Genetics
- Molecular medicine
Background:
- P-selectin is a cell adhesion molecule involved in leukocyte interactions.
- Elevated soluble P-selectin levels are observed in cardiovascular disorders.
- P-selectin gene polymorphisms may influence soluble P-selectin levels and cardiovascular disease risk.
Purpose of the Study:
- To investigate the association between P-selectin gene polymorphisms and serum soluble P-selectin levels.
- To examine the relationship between serum soluble P-selectin levels and coronary artery disease (CAD).
- To explore potential age-dependent effects of soluble P-selectin on CAD.
Main Methods:
- Serum soluble P-selectin levels were measured.
- Three P-selectin gene polymorphisms (C-2123G, A-1969G, Thr715Pro) were genotyped.
- A cohort of 869 CAD patients and 334 healthy controls were analyzed.
Main Results:
- The three P-selectin polymorphisms were strongly associated with serum P-selectin levels, explaining significant variability.
- Genotype distributions did not differ between CAD patients and controls.
- Soluble P-selectin levels showed an age-dependent association with CAD: higher in younger patients (<55 years) and lower in older patients (>65 years) compared to controls.
Conclusions:
- P-selectin gene polymorphisms significantly correlate with serum soluble P-selectin levels.
- A complex, age-dependent relationship exists between soluble P-selectin levels and coronary artery disease.
- Soluble P-selectin may play multifaceted roles in the atherothrombotic process.
Abstract:
P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.