OBJECTIVES: This study aimed to test potential modifying effects of education on the association between apolipoprotein E epsilon4 (Apo E4) and cognitive decline. METHODS: A community cohort(N=683) aged 65 or over completed the Korean version of Mini-Mental State Examination(MMSE-K) at baseline and two years later(1999-2001). Apo E polymorphisms were genotyped, and classified into that with or without Apo E4. Educational levels were categorized into people with or without education. Covariates included demographic(age, gender), life style(smoking, alcohol drinking), clinical (depression, sleep disorder, vascular risk factors) characteristics. RESULTS: The association between Apo E4 and cognitive decline was significant only in the old persons with no education. The interaction term between education and Apo E4 on cognitive decline was significant (p=0.040). CONCLUSION: Elders with no education might be more vulnerable to the impact of Apo E4 on cognitive decline, which suggests gene-environment interaction.
Aged ; Apolipoprotein E4 ; Apolipoproteins ; Apolipoproteins E ; Gene-Environment Interaction ; Humans

The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. Several studies reported that HCV particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. However, the relationship between apoE gene polymorphisms and HCV genotypes in patients with HCV is less well understood. The aim of this study was to investigate the association between apoE gene polymorphism and HCV genotypes in patients. The HCV genotypes were identified among the 124 patients infected with HCV, and the genetic characteristics of the HCV genotype were analyzed. In addition, the results of the clinical laboratory test were comparatively analyzed according to the classified genotypes. Both HCV 1b (n=80) and 2a (n=42) patients had higher AFP, AST, ALT, ALP, γ-GTP, apoB, and apoE values compared with the normal control group. In particular, apoB and apoE levels were statistically significantly higher in the HCV 2a patients (P<0.05) and apoE levels were significantly higher in the HCV 1b patients (P<0.000). According to the results the patients with HCV genotype 1b showed higher values of liver damage related indicators and apoB expression than the patients with HCV genotype 2a. The fat related indicators and apoE expression were not different between the two major HCV genotypes (2a and 1b). We anticipate that the apoE ε3 allele is the most common type in HCV genotype 1b (89.2%) and 2a (91.7%). As a result of apoE genotyping, we confirmed an association with HCV infection and the apoE ε3 allele. However, the ratios of the apoE ε3 allele among the patients with genotype 1b and 2a were similar to each other.
Alleles ; Apolipoproteins B ; Apolipoproteins E ; Apolipoproteins ; Genotype ; Hepacivirus ; Hepatitis C ; Hepatitis ; Humans ; Liver

BACKGROUND: Hypobetalipoproteinemia (HBL) is characterized by plasma concentration of lowdensity lipoprotein cholesterol below the fifth percentile in a healthy population. It has been suggested that HBL may be associated with apolipoprotein E (apoE) and apoB polymorphisms, such as apoB 8344 and apoB EcoRI. METHODS: Patients with HBL (n=51) and age-and- sex-matched healthy controls (n=136) were compared for apoE genotyping, apoB 8344 polymorphism and apoB EcoRI polymorphism. ApoE genotyping and apoB EcoRI polymorphism were determined by polymerase chain reaction (PCR) restriction fragment-length polymorphism. ApoB 8344 polymorphism was determined by the PCR-amplification refractory mutation system. We also Search truncated apoB with ECL western blotting in 23 HBL subjects. RESULTS: We could not find any truncated form of apoB. We found significant elevation of the apoE epsilon2 allele frequency of 0.147 in HBL cases compared with 0.063 in healthy controls (P=0.018). The ApoB 8344 polymorphism showed no significant difference between the HBL and the normal control groups. There were no significant apoB EcoRI allele frequency differences between the HBL and the normal groups. There were no significant apoB EcoRI allele frequency differences between the HBL and the normal groups. CONCLUSIONS: We could not find any relationship between HBL either with apoB 8344 or apoB EcoRI polymorphisms, but apoE epsilon2 allele seemed to be associated with HBL in Koreans.
Alleles ; Apolipoprotein E2 ; Apolipoproteins B ; Apolipoproteins E ; Apolipoproteins* ; Blotting, Western ; Cholesterol ; Gene Frequency ; Humans ; Hypobetalipoproteinemias ; Lipoproteins ; Plasma ; Polymerase Chain Reaction

BACKGROUND: The possible role of apolipoprotein E (APOE for gene, apoE for protein) allele in atherosclerotic diseases is not clearly understood. For the putative role of APOE genotypes, we examined APOE polymorphism among patients with stroke. METHODS: A total of 202 ischemic stroke patients were involved in this study. The genotype DNA was isolated from whole blood and the APOE alleles were determined by polynicrase chain reaction. RESULTS: The genotype of APOE epsilon3/3 was the most common allele in the stroke group and the control group. The frequencies of APOE epsilon2, epsilon3, epsilon4 allele in stroke group were 0.052, 0.851, and 0.097, respectively. There was no significant difference in APOE genotypes between the stroke group and the control group. No significant associations lions were found for the APOE genotypes and the serum lipid profiles. CONCLUSION: These findings suggest that APOE was not related to the stroke,
Alleles ; Apolipoprotein E2 ; Apolipoproteins E ; Apolipoproteins* ; DNA ; Genotype ; Humans ; Lions ; Stroke

BACKGROUND: The determination of apo E polymorphism through the phenotyping is not suitable for large studies in the clinical laboratories because of various problems. So apo E genotyping has been developed. We present a method of apo E genotyping using a modified amplification refractory mutation system(ARMS) technique. METHODS: We used four primers to detect the region containing two mutation points coding amino acid residues 112 and 158 and have developed a method of apo E genotyping by the modified ARMS technique. Apo E genotyping were performed by both the modified ARMS technique and the INNO-LiPA Apo E kit(Innogenetics, Belgium) with the following frequency distribution: Epsilon2/2(n=10), Epsilon3/3(n=15), Epsilon4/4(n=7), Epsilon2/3(n=9), Epsilon2/4(n=12), Epsilon3/4(n=13). RESULTS: All the samples gave the correct and clear amplification patterns. Modified ARMS correctly distinguished among the six apo E genotypes. The apo E genotypes determined by both methods for every specimen studied were in complete agreement. CONCLUSIONS: This modified ARMS technique involved only two stages: PCR and agarose gel electrophoresis. Since apo E genotyping by the modified ARMS is reliable, simple to perform, less time consuming, and not expensive, we conclude that it is suitable for large sample studies in the clinical laboratories.
Apolipoproteins E ; Apolipoproteins* ; Arm* ; Clinical Coding ; Electrophoresis, Agar Gel ; Genotype ; Polymerase Chain Reaction*

BACKGROUND: Currently, several different apolipoprotein E (apo E) genotyping methods have been developed. The Amplification Refractory Mutation System (ARMS) apo E genotyping, as previously described, requires four separate PCR reactions. The purpose of this study is to determine the clinical usefulness of the multiplex ARMS apo E genotyping with the use of only two PCR reactions. METHODS: We used five primers and two separate PCR reactions to detect the apo E polymorphism by using the multiplex ARMS technique. Apo E genotyping was performed with both the multiplex ARMS and INNO-LiPATM Apo E kit (INNOGENETICS) in 122 random samples. We investigated the effect of dimethyl sulfoxide (DMSO) in the multiplex ARMS PCR with various DMSO concentrations (0-15%). RESULTS: All six possible genotypes for apo E were clearly discernible with the multiplex ARMS. The apo E genotypes determined by the two methods were in complete agreement with all 122 samples. We found that DMSO is essential for the successful amplification of the multiplex ARMS and DMSO at concentrations of 3%-7% to be the optimal concentration. CONCLUSIONS: ARMS analysis involves two stages: PCR and agarose gel electrophoresis. Apo E genotyping using the multiplex ARMS requires only two PCR reactions. Thus, because of its simplicity, speed, accuracy, and cost-effectiveness, this method may be appropriate for determining the apo E genotypes in routine clinical laboratories.
Apolipoproteins E ; Apolipoproteins* ; Arm ; Dimethyl Sulfoxide ; Electrophoresis, Agar Gel ; Genotype ; Polymerase Chain Reaction

BACKGROUND: The associations of apolipoprotein E (ApoE) genotypes and cholesterol levels with cognitive decline in Alzheimer's disease (AD) are controversial. The aim of this study is to investigate the individual and combined effects of ApoE epsilon 4 allele (Epsilon4) and cholesterol levels on the progression of AD. METHODS: ApoE genotypes and fasting serum total cholesterol levels were measured in 79 patients with AD. The associations were investigated between Epsilon4, cholesterol level and decline in cognitive function (Korean version of Mini-Mental State Examination) over one year. RESULTS: No prospective individual and combined associations were found between Epsilon4, cholesterol level and decline of cognitive function. Adjustment for age, gender, education, and functional activities of daily living made little difference to the associations. CONCLUSIONS: The cognitive decline of AD might be determined by other factors rather than the impact of Epsilon4 or cholesterol levels.
Activities of Daily Living ; Alleles ; Alzheimer Disease* ; Apolipoproteins E ; Apolipoproteins* ; Cholesterol* ; Education ; Fasting ; Genotype ; Humans

OBJECTIVE: There is recent evidence that insulin resistance is responsible for increasing the risk of developing cognitive dysfunction. To systematically review the influence of intranasal insulin treatment on the cognitive function in Alzheimer's disease patients. METHODS: Randomized controlled trials comparing the cognitive effects of intranasal insulin therapy in Alzheimer's disease patients with controlled interventions were retrieved from Pubmed, Medline, Embase and Cochrane library. Meta-analysis was conducted on the cognitive measurements with a subgroup analysis by dose, gender and apolipoprotein E allele 4 (ApoE ε4) status. RESULTS: Seven randomized controlled trials were eligible for inclusion. Intranasal insulin had a positive influence on the cognitive function as compared to placebo without a statistical significance (standardized mean difference; SMD = 0.109; 95% confidence interval; CI −0.04 to 0.26; P=0.14). In subgroup analysis, a 20 IU dose of intranasal insulin induced a significant improvement in cognitive function (SMD = 0.14; 95% CI 0.05 to 0.24; P=0.004), but 40 IU did not show this effect (SMD = −0.01; 95% CI −0.11 to 0.09; P=0.82). ApoE ε4 positive patients showed a significant decline in cognitive function as compared to ApoE ε4 positive patients in the control group (SMD = −0.213; 95% CI −0.38 to −0.04; P=0.015). Such an effect was not apparent in ApoE ε4 negative patients. Gender had no influence on the cognitive outcomes. CONCLUSION: The results indicate that intranasal insulin may have beneficial effect in improving the cognitive function in Alzheimer's disease patients.
Alleles ; Alzheimer Disease ; Apolipoproteins ; Apolipoproteins E ; Cognition ; Humans ; Insulin Resistance ; Insulin ; Mild Cognitive Impairment

OBJECTIVES: The potential association between choline acetyltransferase(CHAT) polymorphism and the risk of mild cognitive impairment(MCI) has not been investigated in Korea. We examined the main effect of CHAT polymorphism and its interaction with apolipoprotein E(APOE) polymorphism in the development of MCI in elderly Korean sample. METHODS: We analyzed CHAT 2384G > A polymorphism and APOE polymorphism among 149 MCI subjects with MCI and 298 normal controls. We tested the association between MCI and CHAT A allele status using a logistic regression model. In addition, we employed generalized multifactor dimensionality reduction(GMDR) to investigate the interaction between CHAT and APOE with regard to the risk of MCI. RESULTS: The CHAT A allele was associated with AD risk(OR = 1.59, 95% CI = 1.02-2.48, p = 0.042). No significant gene-gene interaction between CHAT and APOE was found in GMDR method(testing balanced accuracy = 0.540, p = 0.055). CONCLUSION: The CHAT A allele was associated with MCI risk in the Korean elderly. Its interaction with the APOE epsilon4 allele was not significant with regard to the development of MCI.
Aged ; Alleles ; Apolipoproteins ; Apolipoproteins E ; Choline ; Choline O-Acetyltransferase ; Humans ; Korea ; Logistic Models ; Mild Cognitive Impairment

OBJECTIVES: The aim of this study was to examine the prospective impact of the apolipoprotein E (APOE) epsilon4 on cognitive performance in the community-dwelling elderly individuals with Alzheimer's disease (AD). METHODS: The total number of subjects was 30 (12 men and 18 women) who were diagnosed with AD from a Korean project of "Early Detection of Dementia". People aged 65-85 years were included in the analysis. The eight neuropsychological domains from the Korean version of Consortium to Establish a Registry of Alzheimer's Disease (CERAD-K) were conducted to test subjects. They have been followed at 24-month intervals with the same assessments at each interval. Their cognitive performance at 2 year intervals was compared by the occurrence of the APOE epsilon4. RESULTS: The impact of epsilon4 allele was significant in the Word List Memory Test (WLMT, F = 4.345, df = 1, p = 0.021) and Word List Recall Test (WLRT, F = 5.569, df = 1, p = 0.033). CONCLUSIONS: The APOE epsilon4 allele was significantly correlated especially with verbal episodic memory domain in community-dwelling elders diagnosed with AD.
Aged ; Alleles ; Alzheimer Disease* ; Apolipoproteins E ; Apolipoproteins* ; Humans ; Male ; Memory ; Memory, Episodic ; Prospective Studies*