관상 동맥 질환에서 아포 E 지단백 유전자 다형성과 혈청 지질치와의 관계 = Correlation between Apolipoprotein E Polymorphysm and Plasma Lipid Levels in Pateints with Ischemic Heart Disease

다국어 초록 (Multilingual Abstract)

Background and aims: The Apolipoprotein E is a ligand of both the protein component LDL receptor as well as the apo E LDL-Receptor related protein (LRP). It modulates the receptor binding of lipoproteins, with the apolipoprotein E found on cell surfaces as its component, thus serving an important role in the lipid metabolism by carrying out the intracellular transport of cholesterol in lipoproteins. The gene for apolipoprotein E is the product of three common genotypes as well as many more rare alleles. The common genotypes are ε2, ε3, and ε4, and are expressed in the three phenotype isoforms of E2, E3, and E4. In the event that E4 is the main component, a rise in the cholesterol level, as the result of down-regulation of the LDL receptor, is observed. Therefore, those samples with E4 genotypes are known to be in much higher risk of coronary artery disease than those with ε3/ε3, while those with ε2 are in low risk (with the exception of hypertiglyceremai Ⅲ). The aim of this study is to analyze in patients with ischemic heart disease the role of aplipoprotein E alleles in order to seek its correlation with coronary artery disease, as well as to seek whether the polymorphism of apo E produces any differences in the severity of coronary artery disease according to plasma lipid levels.
Methods: The subjects for study were 273 patients admitted to the Internal Cardiology Division of the Soonchunhyang University Hospital form December 1998 to February 1999. The subjects were divided into the two groups of which one was ischemic heart disease (IHD) experiment group totaling 105 (avg.60.1 years of age, male/female ratio = 69/36) and the control group totaling 168 (avg. 59.7 years of age, male/female = 73:95). The coronary angiogram was given to 127 subjects, and of this total, 94 have developed significant stenosis in the coronary artery. The stages of the analyzing of the apo E phenotype was first, the separation of DNA from the blood samples, subjecting it to the PCR from with 228 base pairs of expanded products were obtained. The band was determined by means of the reverse hybridization principle on the nitrocellulose strip.
Results: From the 105 patients the distributions of apo E phenotypes were as follows: ε3/2(5.7%), ε4/2(1.9%), ε3/3(70%), ε4/3(20%), ε4/4(1.9%). The relative frequencies of each allele are as follow: ε2 (0.038), ε3 (0.833), ε4 (0.128). The results show as follows:
ⅰ) The IHD experiment group to have a higher occurrence of ε4/3 phenotypes as well as ε4 alleles than the control group.
ⅱ) Both the control group and IHD group showed the largest distribution of ε3/3 for phenotypes, and ε4 for alleles.
ⅲ) The IHD group showed less ε2/3 phenotypes as well as significantly less allele frequency of ε3 in comparison to the control group.
ⅳ) the IHD group showed a much lower level of HDL in comparison to the control group, while the LDL was significantly higher; samples including the apo ε2 showed a significantly higher level of HDL than those without. Among the control group, samples including apo ε2 showed a significantly higher level of TG (triglyceride) than samples without. No significant difference was found between the experiment apo ε4 sample and the control plasma lipid sample.
ⅴ) No significant correlation was found between an apo E polynorphism and the number of involved arteries of a coronary angiogram.
Conclusion: Between the experiment IHD group and control group were found differences in the frequency of alleles. The polymorphism of apo E alleles may contribute as a risk factor to the development of heart disease by involving itself in the metabolism and modulation of plasma lipids.