• Clinical and Experimental Pediatrics
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• 제51권1호
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• pp.42-46
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• 2008

대 상 : Apolipoprotein E (Apo E)는 지단백 대사와 지질의 수송에 중요한 역할을 하는 물질이며 많은 연구들에 의해 Apo E의 다형성이 심혈관계 질환의 중요한 유전 인자임이 알려져 있다. 이에 저자들은 Apo E 의 다형성이 비만 청소년에서 이상 지혈증의 위험도를 증가시키는지를 알아보고자 하였으며 Apo E가 비만 청소년 중에서도 심혈관계 합병증의 위험성이 높은 군을 선별하여 적극적인 치료를 하는 기준이 될 수 있는지를 확인하기 위해 본 연구를 시행하였다. 방 법 : 14-18세의 86명의 비만아(각 연령 및 성별에 따른 체질량 지수[body mass index; BMI] 95백분위수 이상)를 대상으로 하였으며 8시간 금식 후 시행한 혈액검사를 통해 혈당, apolipoprotein (Apo) A1, Apo B, 총콜레스테롤(total cholesterol; TC), 중성지방(triglyceride; TG), 저밀도 콜레스테롤(LDL), 고밀도 콜레스테롤(HDL)을 측정하였고 polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)를 통해 Apo E의 다형성을 검사하였다. 결 과 : 남아와 여아의 비는 1.7이었으며 86명의 평균 나이는 $16.2{\pm}1.8$세이었고 평균 BMI는 $27.4{\pm}2.5kg/m^2$이었다. 유전자 분석에 따른 아형의 빈도(allele frequency)는 ${\varepsilon}2$형이 8.1%, ${\varepsilon}3$형이 87.2%, ${\varepsilon}4$형이 4.7%이었다. Apo E의 유전자형에 따라 ${\varepsilon}2/{\varepsilon}3$와 ${\varepsilon}2/{\varepsilon}3$는 E2군으로 ${\varepsilon}3/{\varepsilon}3$는 E3군, ${\varepsilon}3/{\varepsilon}4$와 ${\varepsilon}4/{\varepsilon}4$는 E4군으로 분류하였고 E2군은 13명(15.1%), E3군은 65명(75.6%), E4군은 8명(9.3%)이었다. 세 군 사이에 나이, 성별, 체중, 키와 BMI는 차이가 없었다. 고지혈증에 대한 검사에서 혈당, Apo A1, TC, TG, HDL은 각 군간 차이를 보이지 않았으며 Apo B와 LDL만이 E4형에서 유의하게 높은 수치를 보였다(P<0.05). 결 론 : 저자들은 본 연구를 통해 비만아에서 Apo E의 유전자형의 빈도를 알 수 있었으며 Apo B와 LDL 농도가 Apo E의 유전자형에 따라 차이가 있음을 확인할 수 있었고 따라서 비만아 중에서도 특정 Apo E4의 유전형을 가진 경우 이상 지혈증의 위험성이 더 높은 것으로 사료된다.

• 대한의생명과학회지
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• 제11권4호
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• pp.429-434
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• 2005

Apolipoprotein E (apoE) restriction isotyping used oligonucleotides to amplify apoE gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on $4\%$ agarose gel. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and] 58cys (E2). DNA was isolated from 72 study participants and apoE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, $38 (52.8\%)$ had apo E4/4 or E3/4 (Group E4), $28(38.9\%)$ had the apo E3/3 genotype (Group E3) and $6(8.3\%)$ had apo E2/2 or E2/3 (Group E2). This genotypic information may help to identify individuals at increased risk for several diseases.

• Journal of Nutrition and Health
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• 제41권5호
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• pp.402-413
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• 2008

This study was performed to investigate Apolipoprotein E phenotypes and the relationship among lipid levels, nutrient intakes, lifestyles and risk factors between subjects with and without hyperlipidemic risk. The data were collected from 675 industrial male workers who had completed annual medical examination. Compared to the normal group, the hyperlipidemic risk group in Apo E3 and E4 had significantly higher BMI (p < 0.05) and showed significantly higher body fat (%), waist circumference and WHR in all types of Apo E (p < 0.05). In addition, the hyperlipidemic risk group had significantly higher total cholesterol, LDL-cholesterol, triglyceride and AI than the normal group in all types of Apo E (p < 0.05). Intakes of protein, calcium, phosphorus, iron, vitamin A, vitamin B1, vitamin B2, vitamin C and niacin in Apo E3 were significantly lower in the hyperlipidemic risk group than in the normal group (p < 0.05). In the logistic regression analysis, after adjustment for other factors, Apo E2 + E4, waist and WHR were the significant risk factors associated with hyperlipidemia, but protein intakes were associated with significantly lower risks of hyperlipidemia (p < 0.05). In conclusion, genetic factor (Apo E2 or Apo E4), anthropometric index and nutrient intake seem to influence hyperlidemic risk. Further studies and efforts will be needed to evaluate the independent relationships among hyperlipidemic risk factors.

• 대한지역사회영양학회지
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• 제13권5호
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• pp.713-722
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• 2008

The purpose of this study was to investigate the association among nutrient intakes and health-related lifestyles with cardiovascular disease risk assessed by blood lipid profile according to Apolipoprotein E genotypes. Middle-aged industrial male workers who had completed their annual medical examination were recruited and data of 675 subjects who finished the nutrient survey were used in the analysis. Anthropometric parameters, dietary assessment (FFQ), health-related lifestyles and blood profiles were used for statistical analyses. Apo E genotype groups were classified into the following three genotypes: Apo E2 group (including E2/E2, E2/E3, E2/E4), Apo E3 group (including E3/E3), Apo E4 group (including E3/E4, E4/E4). The frequency of Apo E2, E3, and E4 allele were 13.3%, 75.0% and 11.7% respectively. There were no significant differences in the anthropometric parameters depending on different Apo E genotypes. Also, no significant differences in the nutrient intakes were found according to the genotype groups. The nutrient intakes of all subjects were similar to or higher than the level of KDRIs (Dietary Reference Intakes For Koreans) except for intakes of calcium (67.44% of KDRIs), vitamin A (73.83% of KDRIs) and vitamin $B_2$ (78.02% of KDRIs). Also, there were no significant differences of health-related lifestyles according to Apo E genotype groups. As for the lipid profiles, Apo E4 group had significantly higher total and LDL-cholesterol concentrations than the Apo E2 group (p < 0.05). We confirmed that plasma total and LDL-cholesterol concentrations were greatly influenced by Apo E genotypes. However, nutrient intakes and health-related lifestyles were not associated with Apo E genotypes.

• Molecules and Cells
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• 제42권11호
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• pp.739-746
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• 2019

Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

• Molecules and Cells
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• 제37권11호
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• Fisheries and Aquatic Sciences
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• 제11권2호
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• pp.88-97
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• 2008

Lipoproteins are complexes of lipids and specific apolipoproteins that are involved in lipid transport and redistribution among various tissues. In this study, we isolated full-length apolipoprotein cDNA sequences encoding apolipoprotein A-I (apoA-I), apoE, apoC-II, and apo-14 kDa in barred knifejaw, Oplegnathus fasciatus. In addition, we reconstructed phylogenetic trees and investigated mRNA tissue distributions. Alignment analyses of amino acid sequences revealed that secondary structures of the polypeptides apoA-I, apoE, and apoC-II in barred knifejaw are well conserved with their teleostean and mammalian counterparts in terms of characteristic tandem repetitive units forming amphipathic ${\alpha}$-helices. Both the sequence alignment data and cleavage sites of apo-14 kDa indicated a clear differentiation between Percomorpha and Cypriniformes. Meanwhile, the phylogenetic trees of apolipoprotein sub-families suggested that the common ancestor prior to the split of the Actinopterygii (ray-finned fishes) and Sarcopterygii (tetrapods) would have possessed the primordial protein-encoding genes. Tissue distribution of each apolipoprotein transcript determined by semi-quantitative RTPCR showed that barred knifejaw apoA-I transcripts were more or less ubiquitously expressed in the liver, intestines, brain, muscle, spleen, and kidney. The most striking difference from previous observations on barred knifejaw was the ubiquitous expression of apoE across all somatic tissues. Barred knifejaw apoC-II showed tissue-specific expression in the liver and intestines, while the liver and brain were the major sites of apo-14kDa mRNA synthesis.

• Childhood Kidney Diseases
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• 제5권2호
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• pp.87-99
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• 2001

목 적 : 본 연구는 소아 미세변화 신증후군 환자와 IgAN에서 apoE 유전자형의 다형성을 알아보고, 스테로이드 반응과 빈발 재발 신증후군에서 apo-E 유전자형의 연관성을 관찰하므로 신증후군 예후인자로의 가능성을 밝히고, 신증후군에서 나타나는 고지질혈증과의 연관성을 알아보고자 하였다. 대상 및 방법 : 43명의 소아 신증후군 환자와 15명의 IgA신병증 한자를 대상으로 apo-E 유전자형을 조사하였다. 대조군은 50명의 혈연관계가 없는 건강한 혈액 공여자를 대상으로 하였다. Genomic DNA는 standard procedure에 따라 말초혈액의 백혈구로부터 분리하였다. 결 과 : 신증후군 환자에서 대조군보다 e4의 빈도가 유의하게 높았다(P<0.01). 그러나 IgAN에서는 e2가 대조군보다 2.6배나 높았다(P<0.01). 빈발재발군 신증후군에서 e4의 빈도가 대조군 보다 4.6배, 비재발군 신증후군 보다 2배 높았다. 특히 e4/4는 빈발 재발군에서만 3명이 발견되었다. apo-E 유전자형에 따른 혈중 알부민, 콜레스테롤, 지질을 비교하였으나 정상 E3군과 E4 변이형에서 유의한 차이는 없었다(P> 0.05). 결 론 :소아 미세변화 신증후군에서 apo-E 유전자형의 연구에서 e4가 대조군 보다 높은 빈도를 보였으며, IgAN에서는 e2와의 연관성을 보였다. e4 유전자형이 특히 빈발 재발군에서 비재발군에서 보다 2배나 높았으며, e4 homozygote는 빈발 재발군에서만 나타나 신증후군의 빈발재발과 스테로이드 의존성의 예후인자의 이용할 수 있으리라 생각된다.

• Journal of Nutrition and Health
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• 제30권8호
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• pp.936-951
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• 1997

As fat consumption has increased in Korea , serum cholesterol concentrations have risen and the prevalence of atherosclerosis increased. The aim of the present study was to investigate the association among apolipoprotein E (Apo E) phenotypes, dietary fat consumption, plasma lipoprotein levels and fatty acid compositions of red blood cells in young healthy women. Seventy-one percent of participants had Apo E3/3, 14.9 percent had ApoE3/2 , 11.8% had Apo E4/3 and 1.2% had Apo E4.2. The subjects daily consumed approximately 1760kcal containing 29 energy % of fat. The ratio of polyunsaturated fat to saturated fat in a diet was 0. 73 . There were no significant differences of nutrient intakes according to Apo E phenotypes. Total cholesterol concentrations of subjects averaged approximately 160mg/dl , but 12 percent of them had over 200mg/dl, which is higher than the range recommended by the National Cholesterol Deucation Program. Notably, most subjects with 210mg/dl had Apo E4 isoforms. Subjects with Apo E4 isoforms had significantly higher total and LDL-cholesterol concentrations than those with Apo E3/2. Also subjects carrying Apo E4 isoforms tended to accumulated more fat in the body. Their BMI , WHR and arm fat area appeared to be how can arm fat area be greater no you mean grater, please check work vsage than subjects with Apo E3 isoforms, but not significantly. Fat intakes slightly influenced serum cholesterol levels. Myristic aicd intakes were positively correlated to serum total and LDL-choelsterol levels. Polyunsaturated fatty acid intakes were negatively correlated to serum total choelsterollevels. The results of 소냐 study suggest that , people with Apo E4 isoforms need to prevent the raising of serum total and LDL -cholesterol concentrations by reducing calorie and fat intakes and by maintaining a normal weight.

• Journal of Korean Neurosurgical Society
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• 제39권1호
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• pp.46-51
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• 2006

Objective : An Intracranial aneurysm is an important acquired cerebrovascular disease that can cause a catastrophic subarachnoid hemorrhage. Atherosclerosis is one of possible mechanism, but its contribution to aneurysm formation is unclear. Human apolipoprotein E[apoE] is best known for its arterial protection from atherosclerosis. In this study we observe apoE expression in experimental cerebral aneurysms of rats to elucidate the role of apoE in the process of cerebral aneurysm formation. Methods : Twenty-four male 7-week-old Sprague-Dawley strain rats received a cerebral aneurysm induction procedure. One month[12] and three months[12] after the operation, the rats were killed, their cerebral arteries were dissected, and the regions of the bifurcation of the right anterior cerebral artery-olfactory artery [ACA-OA] bifurcations were examined histologically and immunohistochemically. Results : In the 1 month group [n=12], the ACA-OA bifurcation showed no aneurysmal change in 7 rats and early aneurysmal change in 5 rats. In the 3 months group (n=12), the bifurcation showed no aneurysmal change in 2 rats and an advanced aneurysm in 10 rats. ApoE expression were in 3 specimen in early aneurysmal change, but not in advanced aneurysms. Conclusion : ApoE expression in early aneurysmal wall suggests a possible role for apoE in early events leading to aneurysm formation. Further studios are necessary to elucidate the exact role of apoE in the pathophysiology of cerebral aneurysm.