Apolipoprotein E polymorphism and severity of angiographically verified coronary artery disease
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Spasojević-Kalimanovska, VesnaKalimanovska-Oštrić, Dimitra
Jelić-Ivanović, Zorana
Topić, Aleksandra
Stanković, S
Stanojević, N
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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.
Keywords:
Allele frequency / Apolipoprotein E polymorphism / Atherogenic allele / Markers of coronary artery disease / Odds ratioSource:
Jugoslovenska medicinska biohemija, 1999, 18, 2-3, 99-105Publisher:
- Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd
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PharmacyTY - JOUR AU - Spasojević-Kalimanovska, Vesna AU - Kalimanovska-Oštrić, Dimitra AU - Jelić-Ivanović, Zorana AU - Topić, Aleksandra AU - Stanković, S AU - Stanojević, N PY - 1999 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/220 AB - 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. PB - Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd T2 - Jugoslovenska medicinska biohemija T1 - Apolipoprotein E polymorphism and severity of angiographically verified coronary artery disease VL - 18 IS - 2-3 SP - 99 EP - 105 UR - https://hdl.handle.net/21.15107/rcub_farfar_220 ER -
@article{ author = "Spasojević-Kalimanovska, Vesna and Kalimanovska-Oštrić, Dimitra and Jelić-Ivanović, Zorana and Topić, Aleksandra and Stanković, S and Stanojević, N", year = "1999", 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.", publisher = "Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd", journal = "Jugoslovenska medicinska biohemija", title = "Apolipoprotein E polymorphism and severity of angiographically verified coronary artery disease", volume = "18", number = "2-3", pages = "99-105", url = "https://hdl.handle.net/21.15107/rcub_farfar_220" }
Spasojević-Kalimanovska, V., Kalimanovska-Oštrić, D., Jelić-Ivanović, Z., Topić, A., Stanković, S.,& Stanojević, N.. (1999). Apolipoprotein E polymorphism and severity of angiographically verified coronary artery disease. in Jugoslovenska medicinska biohemija Društvo medicinskih biohemičara Srbije i Crne Gore, Beograd i Univerzitet u Beogradu - Farmaceutski fakultet, Beograd., 18(2-3), 99-105. https://hdl.handle.net/21.15107/rcub_farfar_220
Spasojević-Kalimanovska V, Kalimanovska-Oštrić D, Jelić-Ivanović Z, Topić A, Stanković S, Stanojević N. Apolipoprotein E polymorphism and severity of angiographically verified coronary artery disease. in Jugoslovenska medicinska biohemija. 1999;18(2-3):99-105. https://hdl.handle.net/21.15107/rcub_farfar_220 .
Spasojević-Kalimanovska, Vesna, Kalimanovska-Oštrić, Dimitra, Jelić-Ivanović, Zorana, Topić, Aleksandra, Stanković, S, Stanojević, N, "Apolipoprotein E polymorphism and severity of angiographically verified coronary artery disease" in Jugoslovenska medicinska biohemija, 18, no. 2-3 (1999):99-105, https://hdl.handle.net/21.15107/rcub_farfar_220 .