• 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.

• 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)

• 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.

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.102-112
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• 2003

The homozygous deletion allele of the angiotensin converting enzyme gene (ACF/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the 4 allele of the apolipoprotein E gene (apoE/4) are reported to be associated with ischemic heart disease. Ischemic cerebrovascular disease (ICVD) is another atherosclerotic disease, and the effects of these polymorphisms on ICVD have been confusing. In this study, I investigated whether ACF/DD, AGN/TT, and apoE/4 genotypes are associated with ICVD and whether genetic risk is enhanced by the effect of one upon another. I ascertained these genotypes in patients with ICVD (n=121) diagnosed by brain computed tomography. Control subjects for the ICVD were randomly selected from subjects matched for age, gender, and history of hypertension with patients. Frequency of ACF/DD genotype was somewhat higher in the patients with ICVD than in the controls (18％ vs. 15％). Incidence of ICVD was higher in subjects with the apoE/4/4 genotype than in the other genotypes (50％ vs. 27-29％). Incidence of ICVD was much higher in subjects with the AGN/TT genotype than in AGN/MM genotype (36％ vs. 17％). Furthermore, the AGN/TT genotype greatly increased the relative risk for ICVD in the subjects with ACF/DD genotype (80.0％ vs. 20.0％, P=0.089). Finally, incidence of ICVD was much higher in the subjects with both apoE/2/4 and AGN/TT genotype than in the other genotypes (83.3％ vs. 16.7％, P=O.095). These results suggest that AGN/TT enhances the risk for ICVD associated with ACF/DD and apoE/2/4.

• Biomedical Science Letters
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• v.11 no.4
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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.

• Korean Journal of Community Nutrition
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• v.13 no.5
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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.

• 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.

• Journal of Sasang Constitutional Medicine
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• v.15 no.1
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• pp.60-71
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• 2003

The purpose of this study was to investigate the effects of medical nutrition therapy(MNT) on plasma lipid levels of hyperlipidemic patients with apo E3 genotype according to Sasang Constitutions. From March to July, 2001, the 33 hyperlipidemic patients admitted to K University Medical Center were studied. The study subjects were classified according to their Sasang constitutions by QSCC II questionnaire which have been used at K University Oriental Medical Center. The anthropometric assessments, blood analysis, and apo E genetic typing were carried out. Nutrient intake was determined by food record method of food taken during two weekdays and one weekend. The MNT including the instruction for hypolipidemic and hypocholesterolemic diet (step l diet) was performed for 12 weeks. The results are as follow; (1) The mean age of hyperlipidemic patients was $49.91{\pm}8.48$ years. (2) The distributions of Sasang Constitution were 60.6% of Tae-eum, 21.2% of So-yang, and 18.2% of So-eum. The distributions of apo E genotype were 6.5% of apo E2/3, 78.8% of apo E 3/3, and 15.2% of apo E 3/4. (3) The nutrient consumption of the apo E3 subjects before the MNT showed lower calorie, iron, calcium, and vitamin B2 intakes than the RDAs for each nutrients with no significant differences among the constitutions. After 12-week of MNT, only the fat consumption was decreased in the Tae-eum group. The MNT did not change the pattern of food intake. (4) The plasma level of triglyceride, total cholesterol, and LDL-C were not changed after MNT in the three constitutional groups. The level of HDL-C was significantly increased significantly in Tae-eum and So-yang group and the level of homocystein was lowered in Tae-eum group after MNT. It could be concluded that the 12-weeks MNT with hypolipidemic and hypocholesterolemic diet did not change the level of total cholesterol, triglyceride, and LDL-C effectively regardless of Sasang constitutions even though the subjects' dietary intake was improved by MNT.

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.25-33
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• 2003

lridology, a form of complementary and alternative medicine (CAM), is the diagnosis of medical conditions through noting irregularities of the pigmentation in the iris. lridological constitution has a strong familial aggregation and is implicated in heredity. Apolipoprotein E (apoE) gene polymorphism is one of the most well studied genetic markers of vascular disease. I investigated the relationship between iridological constitution and apoE polymorphism. I classified 87 hypertensive patients with family history of cerebral infarction and 79 controls according to iris constitution, and determined apoE genotype. Neurogenic type in hypertensives was 32.2% compared with 16.5% in controls (P<0.001). No differences in the apoE genotypes frequencies were observed in patients compared with those in controls ($x^2=0.726$, df-=2, P=0.696). However, in a population with ${\varepsilon}3/{\varepsilon}4$ genotype, the frequency of neurogenic constitution was significantly higher in hypertensives than in controls (60% vs. 0%) ($x^2=5.265$, df=l, P=0.022). These results could imply that apoE ${\varepsilon}3/{\varepsilon}4$ genotype and neurogenic iris constitution are risk factors for hypertension.

• Journal of Nutrition and Health
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• v.40 no.7
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• pp.593-600
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• 2007

Recent studies described the ${\varepsilon}4$ allele of apoE confers a two-to fourfold increased risk for late-onset Alzheimer#s disease (LOAD), but LOAD pathology does not all fit neatly around apo E. Therefore, the goal of this study was to find the association between Alzheimer and apo E4 genotype in the 107 elderly between 50 to 64 years old who visited to FHWC of Sungshin Women#s University. We conducted the questionnaire survey (general & 24 hr dietary recall), anthropometerics (BP, waist & BMI) and blood biochemistry (FBS & lipid profiles). LDL-c and HOMA-IR were calculated by Friedwald#s and Matthew#s formulas. The apo E genotyping was performed by PCR-RFLP method and subjects were divided into three allele groups (${\varepsilon}3$; wild, ${\varepsilon}2$ & ${\varepsilon}4;$ mutants). The apo E allele frequencies were 7.0% for the ${\varepsilon}2$, 83.6% for the ${\varepsilon}3$ and 9.3% for the ${\varepsilon}4$. In comparison with biochemistry characteristics by apo E genotype, FBS was significantly higher in ${\varepsilon}4(129.2{\pm}6.8)$ than that in the others (${\varepsilon}2$: $117{\pm}7.4$, ${\varepsilon}3$: $107.3{\pm}2.2)$ (p<0.01). More than forty percents of ${\varepsilon}4$ group shown the dyslipidemia [high TG (>150mg/dl) & low HDL (<40 mg/dl:male or <50 mg/dl: female)]. The cytokines levels such as IL-1 ${\beta}$, IL-6 and $TNF-{\alpha}$ were not different among three apoE alleles. After the adjusting sex, age & dietary fiber, LDL-c level was siginificantly higher in ${\varepsilon}4$ ($108.3{\pm}7.7$) than that in ${\varepsilon}2$ ($100.4{\pm}8.4$) (p<0.05). According to food intake and the recipe on the basis of 24 hr dietary recall, the elder]y with ${\varepsilon}4$ allele took higher intake frequency of the light -colored vegetable (radish, onion & cabbage) and pan-fried foods (sauteed beef and vegetables, stir-fried vienna with vegetables) than the others. We knew that the elderly with ${\varepsilon}4$ allele had been restricted the calories intakes with high dietary fiber (33.6+2.5 g/d) to maintain the normal level of FBS and LDL-c. On next study, the prevalence of Alzheimer#s disease in this population who has ${\varepsilon}4$ allele on the condition of calories restriction will be continually follow-up.