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INTRODUCTION: Because apolipoprotein E (APOE) genotypes are known risk factors for Alzheimer's disease (AD), they have been measured in clinical trial participants to determine their effect on treatment outcome. METHODS: We determined APOE genotypes in a subset of subjects (N = 415) who participated in a randomized controlled trial of vitamin E and memantine in 613 veterans with mild-to-moderate AD. RESULTS: Similar to the primary study, substudy participants receiving vitamin E also had slower functional decline than those receiving placebo. Overall, there was no difference in the rate of functional decline between APOE ε4 allele carriers and noncarriers. A significant interaction was observed between treatment and the APOE genotype on AD progression: ε4 carriers declined faster than noncarriers in the vitamin E plus memantine treatment arm. DISCUSSION: APOE genotypes may modulate AD treatment response and should be included in the design of future randomized controlled trials.
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Evidences indicate that abnormal lipid metabolism and lipid peroxidation can affect the progression of complications in systemic lupus erythematosus (SLE) patients. Apolipoprotein E (ApoE) and paraoxonase-1 (PON1) play important role in lipid metabolism and protection of lipid peroxidation. The polymorphisms of ApoE and paraoxonase (PON1) L55M (Met < Leu) allele genes lead to disorders in lipid metabolism and are related to atherosclerosis. This study is the first investigation to examine the possible association between ApoE and PON1-L55M polymorphisms and correlation with serum arylesterase (ARE) activities of PON, levels of malondialdehyde (MDA), neopterin, and lipid lipoprotein in SLE patients from Iranian western population. The present case-control study consisted of 107 SLE patients and 101 gender- and age-matched, unrelated, healthy controls from Iran's western population. The ApoE and PON1-L55M genotypes were identified using PCR-RFLP method. The serum level of MDA, neopterin, lipid levels, and ARE activity were determined by HPLC, commercial kits, and spectrophotometry, respectively. Our results showed that ApoE ε4 and PON1-55M alleles act synergistically to increase the risk of SLE by 1.47 times (p = 0.038). We found that the frequency of ApoE Æ3/Æ4 genotype was higher in SLE patients (11.2%) compared with control subjects (5%), although the difference was not significant (p = 0.087). This study for the first time not only demonstrates that ApoE Æ4 and PON-55M alleles synergistically increase the risk of SLE but also reveals that serum levels of MDA, neopterin, and LDL-C are high in SLE patients. This information may be in value for evaluating SLE progression and in the elucidation of the mechanisms of the disease pathogenesis.
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Alelos , Apolipoproteína E4/genética , Arildialquilfosfatasa/genética , Predisposición Genética a la Enfermedad , Lupus Eritematoso Sistémico/genética , Adulto , Hidrolasas de Éster Carboxílico/sangre , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Irán , Lupus Eritematoso Sistémico/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Neopterin/sangre , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
BACKGROUND: Apolipoprotein E (ApoE) is a potential inhibitor of cell proliferation, immune regulation and modulation of cell growth and differentiation; it also has a substantial role in antioxidant activity. ApoE has a potential role in prostate cancer progression. MATERIALS AND METHODS: ApoE genotyping was performed using real-time polymerase chain reaction (RT-PCR) for blood samples from a group of patients with prostate cancer (n=68) and a control group (n=78). RESULTS: The frequency of the E3/E3 genotype was significantly higher in patients compared to controls (p=0.004). E3/E3 genotype carriers were 3.6-fold more likely to be patients than controls (odds ratio=3.67, 95% confidence interval=1.451-9.155; p=0.004). Additionally, the patients with E3/E3 genotype had significantly higher Gleason score (p=0.017), and more patients with this genotype had a Gleason score higher than 7 (p=0.007). Individuals carrying the E4 allele were significantly more common in the control group (p=0.006). The frequency of the E3/E4 genotype was found to be significantly higher in controls compared to patients (p=0.007), and patients were significantly less likely to have this genotype than controls (odds ratio=0.89, 95% confidence interval=0.833-0.967, p=0.007). Individuals carrying the E2/E3 genotype had a significantly lower Gleason score (p=0.049)-all of the patients with this genotype had a Gleason score lower than 7 (p=0.024). CONCLUSION: E3/E3 genotype may be a potential risk factor for prostate cancer and high Gleason scoring. The E4 allele maybe a risk-reducing factor for prostate cancer.
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Apolipoproteína E2/genética , Apolipoproteína E3/genética , Apolipoproteína E4/genética , Biomarcadores de Tumor/genética , Neoplasias de la Próstata/genética , Anciano , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Fenotipo , Neoplasias de la Próstata/patología , Factores Protectores , Factores de Riesgo , TurquíaRESUMEN
Apolipoprotein E genotypes and lipid and lipoprotein levels were determined in hypercholesterolemic and angiographically vertified CHD subjects and compared against 90 normolipidemic controls. The ε4 allele was significantly prevalent in the hypercholesterolemic and CHD subjects. Significant increase in total cholesterol levels in apo ε4 containing subjects were observed in the hypercholesterolemic and CHD group. The study suggests that the ε4 allele by influencing the lipid levels could act as a risk factor for CHD.
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BACKGROUND: An increased frequency of the epsilon4 allele in Alzheimer's disease has been reported, which suggested a functional role of apolipoprotein E isoforms in pathophysiology of Alzheimer's disease. The aims of this study were to determine the frequency of ApoE genotypes in various types of dementia such as Alzheimer's disease, vascular dementia, and Parkinson's disease, to relate epsilon4 and assess risk factors for different types of dementia. METHODS: We assessed the frequency of Apolipoprotein E alleles in 29 patients with Alzheimer's disease, 10 patients with vascular dementia and 9 demented patients with Parkinson's disease. The Apolipoprotein E genotype was determined the polymerase chain reaction (PCR) with sequence-specific oligonuculeotide primers (SSOP) and reverse hybridiza- tion using the INNO-LiPA (Line Probe Assay) Apo E typing kit. RESULTS: Allele frequencies of epsilon2, epsilon3, and epsilon4 were : 0.5, 0.72, and 0.23 in Alzheimer's disease; 0, 0.65, and 0.35 in vascular dementia; 0.6, 0.83 and 0.11 in demented patients with Parkinson's disease. Conculsion : These results indicate that the apolipoprotein E4 allele is associated with not only Alzheimer's disease but also vascular dementia, however not associated with Parkinson's disease. No such an association was observed between the apolipoprotein E alleles and age.