• 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.

• 대한임상검사과학회지
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• 제38권3호
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• pp.179-183
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• 2006

Alzheimer's disease (AD) is characterised neuropathologically by the accumulation of neuritic plaques and neurofibrillary tangles as well as by cerebrovascular amyloid deposition and neuronal cell loss. Current advances have shown the apolipoproteinE-epsilon 4 (ApoE4) allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of ApoE allele frequencies and dementia remains unknown in populations from many countries. We recently initiated a project to examine ApoE frequencies in non-demented healthy Koreans. Genomic DNA in hair root from a thousand persons was collected and ApoE gene type was investigated with the methods of polymerase chain reaction (PCR) and restriction fragment length polymorphism. A group of a thousand non-demented Koreans over the age of 40 years were found to be positive in 15.7% of the cases for ApoE4. AD and ApoE4 were closely related. ApoE epsilon 4 was a dangerous factor of AD and ApoE 4 allele made a contribution to the heterogenicity of AD.

• Journal of Genetic Medicine
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• 제3권1호
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• pp.29-32
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• 1999

The Apolipoprotein E type 4 allele (ApoE ${\varepsilon}4$) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease. The BchE-k variant, which is the common variant of the BchE gene, has been reported to show allelic association with AD in subjects who are also carriers of the ${\varepsilon}4$ allele of the ApoE, especially in subjects over the age of 75. This study was performed to evaluate the distribution of the ApoE and the BchE genotypes in the healthy and AD groups and to evaluate the synergy between the BchE-k variant and the ApoE ${\varepsilon}4$ in AD. The ApoE and the BchE genotypes were determined in DNA samples from 610 healthy people and 60 LOAD patients by using ARMS by standard agarose gel electrophoresis. The effect of the ApoE ${\varepsilon}4$ was closely related to AD(p<0.05). A comparison between the AD patients and the healthy individuals, both with the ${\varepsilon}4$ allele, indicated an interaction between the BchE-k and the ApoE ${\varepsilon}4$(p<0.05). The association of the BchE-k with AD was limited to carriers of the ApoE ${\varepsilon}4$ allele, among whom the presence of the BchE-k gave an odds ratio of AD 3.48 (95% C.I. 1.3-9.2). Therefore, these results suggested that further evidence of an association between the ApoE ${\varepsilon}4$ and LOAD, and the BchE-k acts in synergy with the ApoE ${\varepsilon}4$ as a susceptibility gene for AD.

• 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 Nutrition and Health
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• 제31권9호
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• pp.1411-1421
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• 1998

본 연구에서는 경희의료원 내과에 내원하고 있는 고지혈증 환자를 대상으로 12주 동안 영양상담을 통하여 식사조절을 실시하였으며. 이들 환자들의 apo E 유전자 다형성의 분포양상을 조사하였다 또한 그들의 식습관 분석과 더불어 영양상담 및 교육에 의한 식사조절이 apo E 유전자 다형성에 따라 혈중 지질 농도에 미치는 효과를 관찰함으로써, apo E 유전자 다형성과 식사 조절 후 혈청 지질 농도와의 상호 연관성을 조사하여 다음과 같은 결과를 얻었다. 1) 고지혈증 환자의 apo E 유전자 다형성의 분포양상을 살펴보면 apo E3/3가 70.6% . apo E3/4가 23.5%. 그리고 apo E2/3가 5.8%의 분포를 나타냈다. 일반적 특성인 연령, 몸무게, BMI, %IBW, WHR. 그리고 혈압에서는 apo E 유전자형에 따른 차이가 나타나지 않았으나 12주의 식사조절 후 모든 환자들에서 몸무게, BMI, %IBW, WHR, 그리고 혈압 감소의 경향을 보였다. 2) 고지혈증 환자가 평소 섭취하고 있는 식사 종류는 밥과 면류, 국류, 나물 및 무침류, 구이 및 조림류, 전류 및 볶음요리, 찌게류로 조사되었다. 3) 고지혈증 환자는 영양상담 후 포화지방과 콜레스테롤이 많은 음식의 섭취빈도가 감소하였고, 짠 음식 중 알, 젓갈류의 섭취가 감소하였다. 단음식과 인스턴트 식품의 섭취빈도도 감소하였다. 튀긴음식 섭취와 간식의 빈도도 감소하여 고지혈증 환자를 대상으로 실시한 12주간의 영양상담은 환자들의 식습관과 식품섭취 개선에 좋은 효과를 보였다. 4) 고지혈증 환자의 영양상담 전 식사는 탄수화물 : 단백질 : 지방의 비율이 64.2 : 15.7 : 20.1이었던 반면, 상담 후에는 그 비율이 66.0 : 15.7 : 18.3으로 지방의 섭취비율이 다소 낮아졌다. 또한 영양상담 이전의 콜레스테를 섭취는 236.0mg/day이었으며, 상담 후에는 109.8mg/day로 섭취량이 감소하였다. 5) 영양상담 전의 혈청 LDL-콜레스테롤은 apo E3/4군에서 164.2m조dl, E3/3군에서 133.4mg/dl 그리고 E2/3군에서 112.2mg/dl로 apo E3/4군에서 가장 높았고, 그 다음이 E3/3, 그리고 E2/3의 순으로 나타났으며 , 상담 후 apo E3/4에서 가장 많이 감소하였다. (13.3%) 영양상담 후. 혈청 총 콜레스테롤은 ape E3/4에서 15.6%, E3/3에서 8.5% 감소하였다(p<0.01). 혈청 중성지방과 VLDL-콜레스테를 수준도 모든 군에서 감소하였으며, 특히 3/3군에서 유의성있게 감소하였다. 그러나 HDL-콜레스테를 농도에는 각 군간에 차이없이 증가하는 양상을 보였다. Apo E3/4환자들에서 총 콜레스테롤과 LDL-콜레스테롤이 가장 크게 감소하여 식사조절의 효과가 가장 높은 것으로 나타났다. 6) Apo E 유전자 다형성에 따른 고지혈증환자에서 BMI의 감소량이 클수록 혈청 총 콜레스테를 수준이 비례적으로 감소하였지만(r=0.373, p<0.05), 혈청 중성지방과의 상관관계는 나타나지 않았다. 또한 포화지방의 섭취량이 감소함에 따라 혈청 콜레스테롤농도가 유의적으로 감소하였다(r=0.900, p<0.01).

• Journal of Nutrition and Health
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• 제29권6호
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• pp.642-650
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• 1996

ApoE 유전자의 다형성은 인체 혈중 콜레스테롤 농도의 정상분포를 설명하는 중요한 인자이다. 특히, E2 와 E4 allele들은 고지혈증환자의 혈중에 현저히 나타나며, 각 다른 인종간의 이틀의 상대빈도수가 관상 동맥 질환 유발 위험도와의 상관관계가 아주 높다. Apo E 유전자의 다형성이 혈중 지질 대사변화 에 미치는 영향에 관한 실험은 105명의 건강한 한국여성을 대상으로 시행되었다. Apo E alleles의 한국 인 상대빈도수는 E3가 0.848, E4가 0.087, 그리고 E2는 0.067이었다. 본 연구에서는 E2/2 표현형이 나 타나지 않았지만, 중국 및 일본인과 같이 E4와 E2 allele가 아주 낮았다 최고및 최저혈압, 맥박(p

• 동의생리병리학회지
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• 제18권4호
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• pp.1192-1198
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• 2004

Sasang Constitutional Medicine is a major branch of Korean Traditional Medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, I examined interrelationship among cerebral infarction (CI), apolipoprotein E (apo E) gene polymorphism, and Sasang constitutional classification. Apo E is a key protein modulating the highly atherogenic apoB containing lipoproteins and is a candidate gene for the development of coronary artery disease (CAD). The ε2 and/or ε4 alleles were the first to be implicated in premature CAD, which resulted in this polymorphism being extensively studied. I investigated the association between apo E genotype and CI by case-control study in a Korean population. I also classified CI patients and control group into groups according to Sasang Constitutional Medicine. 218 CI patients and 379 controls without CI were examined. Apo E genotype was determined by 8% polyacrylamide gel separation after DNA amplification. A frequency of apo E ε3/ε3 in the apo E genotype distribution was higher in the CI patients compared with that in controls. Also, it was widely known that Taeumin was easily attacked with CI, but there was no association between apo E polymorphim and Taeumin. However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with apo E ε2 and/or ε4 alleles. No differences in the apo E genotypes frequencies were observed in the Taeumin compared with that in the other constitutions. In addition, I investigated whether the DD(deletion/deletion) or ID(insertion/deletion) genotype of angiotensin converting enzyme (ACE) gene, a candidate gene for CI, was associated with CI, Taeumin constitution, and apo E polymorphism. As a result, the frequency of Taeumin constitution was significantly higher in CI patients with both apo E ε3/ε4 and ACE ID/DD genotypes than in the remaining Sasang constitutions. In summary, it was concluded that the apo E polymorphism is a major risk factor for CI in Koreans and the ACE ID/DD genotype enhanced the relative risk for CI in the subjects with apo E ε3/ε4 genotype and Taeumin constitution.

• 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.

• Preventive Nutrition and Food Science
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• 제2권4호
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• pp.338-347
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• 1997

Apo E polymorphism(e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal vairation in plasma cholesterol concentrations. Both alleles E2 and E4 are significantly more frequent in patients with mixed forms of hyperlipidemia and contribute on the observed differences in CHD risk among different populations. Effects of apo E polymorphism on the distribution of plasma lipid profiles were studied in 89 normolipidemic healthy females, aged 19 up to 22 years. The relative frequencies of E3/3 was 0.787, E3/2 was 0.101, E3/4 allele was 0.112 and no E2/2, E2/4 and E4/4 were found. Weight, height and %LBM were elevated in E2 than those in E3&E4. No differences in the blood pressure among apo E isomers were found, otherwise the pulsation was higher in E4 than that in the others. There were no differences in plasma total-, total DL-, HDL$_3$-, HDL$_2$ cholesterol, apo B-100 and apo A-I, However, phenotype means rank E3/2>E3/3>E3/4 in average TG levels(p<0.0001) significantly, and rank E3/4>E3/3>E3/2 in LDL cholesterol levels. These results were related to the correlation between atherogenic indiced (AI) such as LDL/HDL, (TC-HDL)/HDL, HDL$_3$/HDL$_2$. The ratio of HDL$_3$& HDL$_2$was significantly increased in E2 & E4 than that in E3(P=0.043). LCAT activity was not different between E2 and E3 but was highly increased in E4 (p<0.0001 among apo E isomers), but CETP was not different. Since the negative correlation between LCAT and CETP in apo E2(r=-0.491) was stronger than that in apo E3, E2 allele impacts the clearance of plasma apo E mediated lipoproteins. In conclusion firstly, E4 mediated alteration through LDL or E receptors results in lower TG or higher $\beta$-lipoprotein levels and E2 shows reciprocal effects of E4, respectively. Second, E4 allele was more atherogenic than E2 allele because the higher levels of AI such as HDL$_3$/HDL$_2$ were criticized.

• Advances in Traditional Medicine
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• 제4권2호
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• pp.104-111
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• 2004

Sasang Constitutional Medicine is a major branch of Korean Traditional Oriental Medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, we examined interrelationship among cerebral infarction (CI), apolipoprotein E (apoE) gene polymorphism, and Sasang constitutional classification. ApoE is a key protein modulating the highly atherogenic apoB containing lipoproteins and is a candidate gene for the development of coronary artery disease (CAD). The ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles were the first to be implicated in premature CAD, which resulted in this polymorphism being extensively studied. We investigated the association between apoE genotype and CI by case-control study in a Korean population. We also classified CI patients and control group into groups according to Sasang Constitutional Medicine. 196 CI patients and 379 controls without CI were examined. ApoE genotype was determined by 8% polyacrylamide gel separation after DNA amplification. A significant difference in the apoE genotype distribution was observed in the CI patients compared with that in controls ($X^{2}$=14.920, df=4, P=0.005). Also, the frequency of Taeumin constitution in patients with CI was significantly higher than that in controls (58.0% vs. 36.9%; P<0.001). However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with apoE ${\varepsilon}2\;and/or\;{\varepsilon}4$ alleles. No differences in the apoE genotypes frequencies were observed in the Taeumin compared with that in the other constitutions. In addition, we investigated whether the DD genotype of angiotensin converting enzyme (ACE) gene, a candidate gene for CI, was associated with CI, Taeumin constitution, and apoE polymorphism. As a result, the frequency of Taeumin constitution was significantly higher in CI patients with both apoE ${\varepsilon}3/{\varepsilon}4$ and ACE ID/DD genotypes than in the remaining Sasang constitutions (14.5% vs. 8.3% and 0%) ($X^{2}$=13.521, df=6, P=0.035). In summary, we concluded that the apoE polymorphism is a major risk factor for CI in Koreans and the ACE ID/DD genotype enhanced the relative risk for CI in the subjects with apoE ${\varepsilon}3/{\varepsilon}4$ genotype and Taeumin constitution.