Apolipoprotein E polymorphism and severity of angiographically verified coronary artery disease

Abstract

Apolipoprotein E is an important genetic determinant of serum lipoprotein concentrations and coronary artery disease risk. The apo E polymorphism is a major determinant of interindividual variation in the initiation and progression of atherosclerosis. Differences in the gene sequence cause structural changes strongly affecting binding properties of the corresponding apo E isoforms. The presence of the epsilon 2 allele leads to LDL receptor upregulation and increased LDL clearance. In contrast the presence of the epsilon 4 allele leads to receptor down regulation and decreased LDL clearance. For most populations, individuals with the apo epsilon 2 allele display lower levels of plasma cholesterol compared with individuals carrying the apo epsilon 3 allele, whereas individuals with the apo epsilon 4 allele show higher levels of plasma cholesterol, especially LDL-cholesterol and an increased risk for cardiovascular disease. ApoE polymorphism explains near 7% of the variation in total, LDL cholesterol and apo B levels. To examine whether the polymorphism in the apo E gene is associated with CAD in our population, we analyzed 94 patients with angiographically verified CAD and in 45 patients with excluded CAD as a control group. The apo E phenotype was determined with isoelectric Focusing and Western immunoblotting technique using commercial antibodies. Patients were divided into three groups according to arteriograms as category: 1. mild, evidence of narrowing of one coronary artery >60% (39); 2. moderate, narrowing of two major coronary arteries (30) and 3. Severe, narrowing of all three major coronary arteries (25). The apo E allele frequencies of patients with CAD vs without CAD were 4.2% vs 7.7% For epsilon 2; 86.7% vs 85.5% for epsilon 3 and 9.1% vs 6.6%; for epsilon 4. The frequency of allele epsilon 4 was higher in patients with 3 vessel CAD than in patients without CAD (12% vs 6.6%) but it did not reach the statistical significance (chi(2)= 0.83, p = 0.36, d.f. 1). The Odds ratio for risk of CAD associated with the presence of apo epsilon 4 allele was 1.39 and for the phenotype E3/4 1.60. Our preliminary results suggest that the presence of apo epsilon 4 allele may impose some risk for developing CAD and that apo E determines the severity of CAD.