• Journal of Nutrition and Health
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• v.33 no.6
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• pp.639-646
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• 2000

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.1
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• pp.225-232
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• 1999

Apo E polymorphism(e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal variation in plasma cholesterol concentrations. Among 62 normolipidemic healthy females, aged 19 up to 22 years, the relative frequencies of E3/3 was 0.806(n=50), E3/2 was 0.081(n=5), E3/4 allele was 0.113(n=7), and no E2/2, E2/4 and E4/4 were found. Based on the five samples of E2 allele, five subjects were randomly selected by E3 and E4 groups for the study of effects of apo E polymorphism on the distribution of serum lipid and amino acids profiles. No differences in the anthro pometric data 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 HDL , HDL3 , HDL2 & LDL cholesterol, and apo A I concentrations. However, phenotype means significantly rank E2>E3>E4 allele in average TG levels(p=0.014), and rank E4>E3>E2 in total cholesterol levels(p=0.011). Atherogenic index(AI) such as lipoproteins was significantly increased in E2 & E4 than that in E3(p=0.045). Subjects with E3/2 allele had significantly higher concentrations of glutamine, phosphoserine and taurine, while subjects with E3/4 allele showed significantly lower concentrations of arginine and am inobutyrate and elevated level of phosphoserine in plasma com pared to those of E3/3 allele. Higher level of plasma taurine in subjects with E3/2 or E3/4 allele appears to be related to the elevated level of plasma total and LDL cholesterol concentrations compared to those of E3/3 allele.

• The Journal of Korean Medicine
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• v.25 no.4
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• pp.209-219
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• 2004

The author investigated whether ACE/DD, AGN/TT, and ApoE/ε4 genotypes are associated with CI and whether genetic risk is enhanced by Sasang constitutional classification. The author ascertained these genotypes in patients with CI (n=211), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. However. there was significant association between ApoE polymorphism and CI (x²=15.089, p<.05). Furthermore, frequency of AGN/TT genotype was higher in the patients with CI than in the controls (x²=20.072, p<.05). The frequency of T allele Was 0.91 in patients and 0.82 in controls (x²=17.237, p<.05). However, the Sasang constitutional classification did not increase the relative risk for CI in the subjects with ApoE/ε4 or AGN/T allele. These results suggest that ApoE and AGN polymorphism predict CI. but Sasang constitutional classification does not enhance the risk for CI associated with ApoE/ε4 or AGN/TT in a Korean population.

• Advances in Traditional Medicine
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• v.4 no.2
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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.

• Preventive Nutrition and Food Science
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• v.2 no.4
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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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• v.6 no.4
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• pp.312-318
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• 2006

The association between apolipoprotein E (apoE) gene polymorphism and ischemic cerebrovascular disease (ICVD) has been controversial. These controversies may be due to inaccurate classification of patients and ethnic differences. The aim of the present study was to assess the relationship between apoE gene polymorphism and the development of ICVD in a population from Korea. We investigated 136 patients with ICVD and 357 controls without ICVD. No differences in the apoE genotypes frequencies ($X^{2}$ = 3.660, df = 5, P = 0.454) and even in the alleles frequencies ($X^{2}$ = 1.946, df = 2, P = 0.378) were observed in the ICVD patients compared with that in controls. The data have been compared with data found in other population groups. However, the risk of ICVD associated with apoE ${\varepsilon}3/{\varepsilon}4$ genotype was increased nearly 3-fold in subjects possessing the history of diabetes mellitus (OR 3.3, 95% CI 1.2-9.4, P = 0.026). We concluded that the apoE polymorphism is not associated with ICVD at least in the Korean population, but the apoE frequencies found in this study differ significantly from those obtained in Japanese.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.87-99
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• 2001

Purpose: We studied to find out apo-E genotype polymorphism in minimal change nephrotic syndrome(MCNS) and IgA nephropathy(IgAN) and to determine the relationship between apo-E genotype and clinical course of MCNS. Materials and Method: 43 MCNS patients and 15 IgAN patients were examined for apo-E polymorphism. 50 healthy blood donors were examined for apo-E genotype as control. Genomic DNA was prepared front peripheral blood leukocytes according to standard procedures. Results: As compared with control group, e4 allele frequency was significantly increased in MCNS (p<0.01). However, in IgAN e2 allele frequency, however, was 2.6 times higher than normal control (P<0.01). The frequency of e4 allele of frequent relapser group was 4.6 times higher than normal control and was 2 times higher than infrequent relapser group. Conclusion: We think that apo-E typing might be one of the parameters, which should be considered to predict the course of MCNS in children. MCNS with risky HLA profile and E4/4 genotype could indicate the need for a longer steroid administration. And apo-E genotype needs to be considered for the evaluation of therapeutic responses to other drugs. (J, Korean Soc Pediatr Nephrol 2001 ; 5 : 87-99)

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.113-119
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• 2003

The association between apolipoprotein E (apo E) gene polymorphism and ischemic cerebrovascular disease (ICVD) has been controversial. These controversies may be due to inaccurate classification of patients and ethnic differences. We investigated the association between apo E genotypes and ICVD patients by case-control study in a Korean population. The association between apo E polymorphism and ICVD was examined in 121 patients with ICVD and 132 controls without ICVD. The E3/E4 phenotype was more frequent in control subjects (23.8％) than in patients (13.0％) (p<0.05). The E2/E3 phenotype was more frequent in patients (14.8％) than in control subjects (10.8％), but the difference was not statistically significant (p>0.05). These results suggest that the E4 allele may be a protective factor against early vascular morbidity, and the E2 allele may be a risk factor for cerebrovascular morbidity.

• Journal of Nutrition and Health
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• v.29 no.6
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• pp.642-650
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• 1996

Apo E polymorphism (e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal variation 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 105 normolipidemic healthy women. The relative frequencies of common alleles for gene locus of apo E in this study were that E3 allele was 0.848, E4 allels was 0.087, and E2 allele was 0.067. SBP and DBP were slightly more elevated in E2 allele than those in E3 and E4. The pulsation was also significantly (p<0.016) increased by E2 allele with excess body fat % in E2 allele. There were no differences in total-, total HDL-, VLDL+LDL-, VLDL- and LDL cholesterol among the apo E alleles. However, apo E2 allele subject had lower level of total HDL and HDL2 cholesterol (P<0.047) and significantly higher lev디 of HDL3 cholesterol (P<0.05) than those in apo E3 and E4 allele subject. The conclusion is that first, it seems that apo E4-mediated alteration through LDL B/E receptors or E receptors in cholesterol metabolism results in lower plasma TG or remanate particles and in higher levels of VLDL+LDL or LDL. Second, apo E2 allele shows reciprocal effects of E4 on the plasma lipid metabolism, respecitvely. Third, apo E2 allele was more atherogenic than apo E4 because the higher levels of HDL3/HDL2 ratio and atherogenic index[(TC-HDL)/HDL]were criticized.