Association between Apolipoprotein E Genotype and Treatment Response in Chronic Hepatitis C / 대한임상미생물학회지

BACKGROUND: Hepatitis C virus (HCV) causes a chronic infection, resulting in progressive liver damage. Recent studies have described the protective effect of the apolipoprotein E (ApoE) genotype on liver damage in cases of HCV infection. Their findings were explained by the influence of the ApoE genotype on HCV pathology, which seems to be integrally linked to the process of HCV uptake into hepatocytes. We investigated whether specific ApoE genotypes were associated with the different clinical aspects of HCV infection in patients with chronic HCV. METHODS: From the whole blood of 196 chronic HCV hepatitis patients, the ApoE genotypes were determined by an allele-specific polymerase chain reaction. Several markers, including liver enzymes, platelet counts and HCV viral loads, as well as the radiologic findings, were investigated. In order to estimate the treatment outcome, the sustained virologic response (SVR), early virologic response (EVR) and end-of-treatment response (ETR) were determined according to the HCV viral loads. RESULTS: Based on genotyping, 15.8% (n=31) of the patients had the ApoE E4 allele (E2/E4, E3/E4, E4/E4), while 84.2% (n=165) were missing the ApoE E4 allele (E2/E2, E2/E3, E3/E3). Several clinical results of the E4-positive group, including liver enzymes, albumin, platelet counts, HCV viral loads and hepatic coarseness were not significantly different from those of E4-negative group. There were no differences in the SVR, EVR and ETR between patients with the ApoE E4 allele and those without the ApoE E4 allele. CONCLUSION: There was no significant effect of the ApoE genotype on the clinical aspects of HCV infection and the anti-viral response, including SVR, EVR and ETR, in chronic HCV hepatitis patients.

Association of Apolipoprotein E Gene Polymorphism With Cognitive Function of the Elderly Residents in a Rural Community

BACKGROUND: It is not clear whether polymorphism of the apolipoprotein E (ApoE) gene influences the cognition of community residents. The aim of this study was to establish the association between ApoE gene polymorphism and cognitive function in an elderly rural community in Korea. METHODS: A total of 388 subjects aged 65 and over were recruited. Demographic characteristics, past history of illness, and scores on the Korean version of the Mini Mental State Examination (K-MMSE), the Geriatric Depression Scale . Short Form (GDS-S), and the Korean version of Instrumental Activities of Daily Living (K-IADL) were evaluated. The lipid profile and ApoE genotype were sampled from 377 of the participants. RESULTS: Of the entire cohort, 75% had less than 6 years of education, and 30% were illiterate. The frequencies of the ApoE epsilon2, ApoE epsilon3, and ApoE epsilon4 alleles were 48 (6.6%), 372 (86.9%), and 49 (6.5%), respectively. The K-MMSE score was much lower in those with two ApoE epsilon3 alleles than in those with only one ( p=0.046). However, the numbers of ApoE epsilon2 alleles (p=0.976) and ApoE epsilon4 alleles (p=0.934) carried by the individual were not associated with K-MMSE score. Both K-IADL (p<0.001) and GDS-S (p<0.001) scores were significantly correlated with K-MMSE score. Grouping of the participants into three groups according to K-MMSE score (i.e., 0-17 , 18-24, and 25-30) also revealed that this score was correlated with K-IADL score (p<0001), GDS-S score (p<0.001), and the ApoE epsilon3 allele (p=0.035). CONCLUSIONS: These results suggest that the ApoE epsilon3 allele has a negative influence on cognitive function (K-MMSE) in this rural community. Surprisingly, we were unable to detect any relationship between the ApoE epsilon4 allele and cognitive function. There was a positive correlation between K-MMSE, K-IADL, and GDS-S scores.

Severity of Disability and Serum Lipid Level according to the Genotype of Apolipoprotein E in Patients with Brain Injury

OBJECTIVE: This study was to investigate the relationship between genotype of Apolipoprotein E (Apo E) and severity of disability after brain injury as well as serum lipid profile. METHOD: One hundred thirty-five brain injured patients (mean age 54.6 16.7 years, 90 male and 45 female) were enrolled. There were 34 patients with ischemic Stroke, 61 hemorrhagic stroke, and 40 traumatic brain injury. Apo E genotype was determined by polymerase chain reaction and polyacrylamide gel electrophoresis. The serum concentra tions of total cholesterol, triglyceride, and HDL-cholesterol were measured. The outcome of brain injury was assessed by functional independence measure (FIM) scores. RESULTS: Most frequent Apo E genotype was E 3/3 (72%). In hemorrhagic stroke patients with Epsilon4 allele, FIM score at admission was significantly lower than that of the patients without Epsilon4 allele (p<0.05). In traumatic brain injury patients with Epsilon4 allele, FIM score change was significantly smaller than that of patients without Epsilon4 allele (p<0.05). The level of total serum cholesterol was lower in the ischemic stroke patients who have Epsilon2 allele in comparison with the patients without that allele. CONCLUSION: The presence of Epsilon4 allele is considered to have relationship with the severity of disability and functional outcome in the patients with brain injury.

Rapid Apolipoprotein E Genotyping by the Multiplex Amplification Refractory Mutation System / 대한임상병리학회지

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.

Serum Lipid Profile and Prognosis of Stroke Patient according to Genotype of Apolipoprotein E

OBJECTIVE: To determine allele frequencies of apolipoprotein (Apo) E according to the type of stroke in Korean and to investigate the relationship between the Apo E genotype and serum lipid profile as well as outcome after stroke. METHOD: Fifty-eight stroke patients admitted between January and December 1999 were enrolled. The serum concentrations of total cholesterol, triglyceride, and HDL-cholesterol were measured. The LDL-cholesterol concentration were calculated by Friedwald formula. Apo E genotypes were determined by polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE). The outcome of stroke was measured by functional independence measure (FIM) scores. RESULTS: Most frequent Apo E genotype was E 3/3 (72%), followed by E 3/4 (17%), E 2/3 (9%) and E 2/2 (2%). The level of total serum cholesterol and LDL-cholesterol were lower in the stroke patients who have (epsilon)2 allele in comparison with the patients without that allele. (epsilon)4 allele does not influence on the outcome of stroke patients measured by FIM. CONCLUSION: Most frequent Apo E genotype was E3/3. (epsilon)2 allele influenced on the serum cholesterol level in stroke patients. However, (epsilon)4 allele does not correlate with worse prognosis in stroke patients in this study.

Influence of Apolipoprotein E Polymorphism into Alteration of Atherosclerotic Cardiovascular Disease in CAPD Patients / 대한신장학회잡지

Specific apolipoprotein (apo) E genotype has been suggested as a risk factor for atherosclerosis in the general population. Lipid metabolism is known to be modulated by apo E genotype. In this study, we measured apo E genotype, lipoprotein (a)[Lp (a)], apo A phenotype and other lipoproteins in 50 CAPD patients, and evaluated the association of lipid parameters with atherosclerotic cardiovascular disease. Dipyridamole thallium scan with SPECT and ankle- arm blood pressure index (AABI) were performed in all the subjects. The patients who had positive finding in at least one of the two test were considered to have atherosclerotic cardiovascular disease [CVD (+)]. Fifteen patients had evidence of cardiovascular disease. Serum Lp (a) concentration (median; interquartile range) of CVD (+) patients (n=15, 62.0 mg/dl; 29.5-82.3) was not different from that of CVD (-) patients (n=35, 65.1mg/dl; 34.3-89.9). The frequency distribution of apo (a) phenotype of CVD (+) patients did not differ from that of CVD (-) patients. In addition, there were no differences of other lipoproteins levels and lipid profiles between two group. However, significant difference in the frequency distribution of apo E genotype (E2; 6.7 vs 20%, E3; 40 vs 68.6%, E4; 53.3 vs between CVD (+) and CVD (-) patients. After stratifying the subjects according to the apo E genotype, we observed no difference of lipid profiles, apolipoproteins and Lp (a) concentration in E2, E3, E4. Multivariate regression analysis of risk factors for CVD revealed age and the presence of apo E4 phenotype as independent risk factors of atherosclerotic cardiovascular disease. In conclusion, Apo E4 genotype could be an independent risk factor of atherosclerotic cardiovascular disease in CAPD patients.

The apolipoprotein E genotyping using the PCR-RFLP was useful to linkage analysis of Alzheimer's disease families

Apolipoprotein E (ape E) has three common alleles (ape epsilon 2, epsilon 3 and epsilon 4) that code for three major isoforms E2, E3 and E4. The isoforms differ from each other by a single amino acid substitutions at two positions and also differ in their binding affinity for the apo E receptors. Moreover, recently a strong association between the apo epsilon 4 allele and late-onset Alzheimer disease (AD) was demonstrated. In this study, were analyzed the apo E genotypes using the Hhal digestion of PCR amplified samples, and the apo epsilon 4 allele frequency from 70 AD patients and 106 normal population in Korea. The results suggested that the frequency of epsilon 4 allele among the AD patients (35.7%) was 3 times higher than that among the control population (13.7%). The data, which are in agreement with recent reports, suggests that the apo epsilon 4 allele is associated with AD in Korea.

Determination of the apolipoprotein E genotype using PCR-RFLP in kidney diseases.

Using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), genotypes of the apolipoprotein E (Apo E) were determined in 50 control subjects and 60 Thai kidney diseases patients including nephritic syndrome and chronic renal failure (CRF) (30 each). Exon 4 of the Apo E genomic DNA was amplified between nucleotide numbers 2849 and 3071 (270 base pairs) then digested with HhaI. It is observed that E3/3 was the most common genotype found in the control subjects (80%). In nephritic syndrome patients, E4/3 was found to be the most frequent (53.3%). On the contrary, E3/3 was found to be the most prominent in CRF patients (80%). There was a significant different of the Apo E genotype in hephrotic syndrome from the normal control subjects (p < 0.05 by X2 analysis). One the other hand, there was no significant difference of the Apo E genotype in CRF patients from the control subjects (p>0.5). Cholesterol and triglyceride levels of the E4/3 nephrotic syndrome patients were significantly different from the normal controls of the same genotype (p<0.05). Similarly, in CRF patients, triglyceride level of the E3/3 genotype was also significantly different from the normal controls of the same genotype (p<0.05). These results suggested that polymorphism of the Apo E genotypes may be associated with the lipid abnormalities in renal diseases.