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Braz. j. med. biol. res ; 54(2): e10098, 2021. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1142576


We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.

Humans , Aged , Aged, 80 and over , Apolipoproteins E/genetics , Exercise , Cognition , Polymorphism, Genetic , Quality of Life , Alleles , Alzheimer Disease/genetics , Genotype
Article in English | WPRIM | ID: wpr-887515


INTRODUCTION@#The apolipoprotein E (@*METHODS@#We classified the @*RESULTS@#The baseline serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lower in carriers of @*CONCLUSION@#Polymorphism in the

Apolipoproteins E/genetics , Atherosclerosis/genetics , Cardiovascular Diseases , Genotype , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipids
Article in Chinese | WPRIM | ID: wpr-921679


In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)-based liver metabolomics approach was used to explore the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in improving atherosclerosis(AS) of mice with apolipoprotein E gene knockout(ApoE~(-/-)). AS mouse model was induced by high-fat diet. The pathological and biochemical indexes such as the histopathological changes, body weight, liver weight, blood lipid level and inflammatory factors in the liver of mice were determined. The metabolic profiling of mice liver samples was performed with UPLC-Q-TOF-MS. Multiple statistical analysis methods including partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to screen and identify biomarkers. The levels of related enzymes including LCAT, sPLA2, EPT1 and ACER1 were detected. The results showed that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" significantly reduced the areas of aortic plaque and fat vacuoles of liver in AS mice and decreased the accumulation of lipid droplets and liver coefficient. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" also regulated the levels of blood lipid and inflammatory injury in the liver. The metabolites of the control group, the model group and the "Trichosanthis Fructus-Allii Macrostemonis Bulbus" group could be distinguished significantly. Fifteen potential biomarkers related to AS were discovered and preliminarily identified, seven of which could be regulated by "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in a trend of returning to normal. Metabolic pathway analysis screened out two major metabolic pathways. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" obviously regulated the levels of LCAT, sPLA2, EPT1 and ACER1. It was inferred that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" could play a major role in AS treatment by regulating glycerophospholipid and sphingolipid metabolism disorders in the liver, with the mechanism probably relating to the intervention of the expression of LCAT, sPLA2, EPT1 and ACER1.

Animals , Apolipoproteins E/genetics , Atherosclerosis/genetics , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Liver , Metabolomics , Mice
Acta Physiologica Sinica ; (6): 42-50, 2021.
Article in Chinese | WPRIM | ID: wpr-878234


This study was designed to evaluate the role of short-chain fatty acid butyrate acid on intestinal morphology and function, and atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE

Animals , Apolipoproteins E/genetics , Atherosclerosis/prevention & control , Butyrates/pharmacology , Caco-2 Cells , Diet, High-Fat/adverse effects , Fatty Acids, Volatile , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Plaque, Atherosclerotic
Braz. j. med. biol. res ; 54(4): e9764, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153532


Naringenin (NAR) is a major flavanone in citrus fruits that has multiple pharmacological attributes such as anticancer and antiatherogenic. This study aims to investigate the mechanism of NAR in high-fat-diet (HFD)-induced atherosclerosis (AS) in apolipoprotein E-knockout (ApoE-/-) mice. A HFD-induced AS ApoE-/- mouse model was established. The mice were treated with HFD, different doses of NAR and simvastatin (Simv). After drug treatment, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), and alanine aminotransferase (ALT) were determined. The expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected using qRT-PCR and enzyme-linked immunosorbent assay. The plaque area of the aorta of AS mice was determined using oil red O staining. Western blot analysis was applied to measure the levels of autophagy-related proteins [protein 1 light chain 3B (LC3B), beclin 1, and p62]. The TC, TG, LDL-C, TNF-α, ALT, and MDA levels were significantly increased while the HDL-C, SOD, and GSH-Px levels were decreased in the HFD-induced AS ApoE-/- mice. NAR treatment reversed the expression of the above indicators in mice. After they were treated with different doses of NAR, the LC3B and beclin 1 levels were improved while the p62 protein level was decreased. This study suggested that NAR could promote cell autophagy to improve HFD-induced AS in ApoE-/- mice.

Animals , Rabbits , Flavanones/pharmacology , Atherosclerosis/drug therapy , Apolipoproteins E/genetics , Autophagy
Repert. med. cir ; 30(2): 134-141, 2021. tab.
Article in English, Spanish | LILACS, COLNAL | ID: biblio-1362701


Introducción: la apolipoproteína E (APOE) es una glicoproteína implicada en el transporte de moléculas lipídicas. Se han descrito tres alelos del gen APOE: Ɛ2, Ɛ3 y Ɛ4. Varios estudios demuestran asociación de la isoforma APOE4 con Alzheimer de inicio tardío. Objetivos: determinar las frecuencias genotípicas y alélicas del gen APOE en una muestra de adultos en Bogotá. Materiales y métodos: estudio observacional descriptivo de corte transversal. A partir de una muestra de sangre periférica se extrajo ADN genómico y se realizó PCR-Tetraprimer para la determinación de los alelos de APOE. Resultados: se incluyeron 1.254 sujetos, 942 mujeres (75%) y 312 hombres (25%) con edades entre 40 y 100 años. El alelo más frecuente fue el Ɛ3 (85%), seguido por Ɛ4 (11%) y Ɛ2 (2%). De la población que manifestó tener ascendencia cundiboyacense, 567 sujetos (74.6%) presentaban el genotipo Ɛ3/Ɛ3, mientras que 156 (20.4%) el Ɛ3/Ɛ4, 23 (3%) el Ɛ2/Ɛ3, 11 (1.5%) el Ɛ4/Ɛ4y 4 (0.5%) el Ɛ2/Ɛ4. Los individuos con genotipoƐ2/Ɛ2 manifestaron no conocer el dato de ascendencia. Conclusiones: las frecuencias alélicas y genotípicas de APOE varían según el origen étnico, sin embargo es posible la identificación de sujetos con el genotipo menos frecuente (Ɛ2/Ɛ2) al analizar muestras de mayor tamaño. En los reportes previos en el país no se ha descrito el genotipo Ɛ2/Ɛ2, el cual fue identificado en la presente muestra como el de menor proporción.

Introduction:apolipoprotein E (APOE) is a glycoprotein involved in the transport of lipid molecules. Three alleles of the APOE gene have been described: Ɛ2, Ɛ3 and Ɛ4. Several studies show an association of the APOE isoform with late-onset Alzheimer ́s disease. Objectives: to determine the genotypic and allelic frequencies of the APOE gene in an adult sample in Bogotá. Materials and Methods: a cross-sectionalobservational descriptive study. Genomic DNA was extracted from a peripheral blood sample and APOE alleles and genotypes were determined using the PCR tetra-primer method. Results:we included 1254 subjects, 942 women (75%) and 312 men (25%) aged between 40 and 100 years. The most frequent allele was Ɛ3 (85%), followed by Ɛ4 (11%) and Ɛ2 (2%). Of the population that declared to have Cundinamarca and Boyacá sub-regions ancestry, 567 subjects (74.6%) had genotype Ɛ3/Ɛ3, while 156 (20.4%) hadƐ3/Ɛ4, 23 (3%) Ɛ2/Ɛ3, 11 (1.5%) Ɛ4/Ɛ4and 4 (0.5%) had genotype Ɛ2/Ɛ4.The individuals with genotype Ɛ2/Ɛ2 declared not to know the data on their ancestry. Conclusions: the allelic and genotypic frequencies of APOE vary according to ethnic origin. However identifying subjects with the less frequent genotype (Ɛ2/Ɛ2) is possible when analyzing larger samples. In previous reports in the country, genotype Ɛ2/Ɛ2, has not been described and was identified in the present sample as the one with the lowest proportion.

Humans , Male , Female , Middle Aged , Apolipoproteins E , Polymerase Chain Reaction , Alzheimer Disease , Polymerase Chain Reaction , Protein Isoforms
Arq. bras. cardiol ; 115(5): 873-881, nov. 2020. tab, graf
Article in Portuguese | SES-SP, LILACS, SES-SP | ID: biblio-1142278


Resumo Fundamento: O conhecimento dos fatores ambientais e genéticos para um envelhecimento bem-sucedido em idosos longevos é controverso. Acrescenta-se a esta evidência, o fato de serem poucos os estudos delineados com essa população. Objetivo: Investigar a relação entre os genótipos mais frequentes da apolipoproteína E (APOE) e a mortalidade em idosos longevos que vivem em comunidade e sua sobrevida de acordo com os fatores de risco cardiovascular. Métodos: Uma amostra de 74 idosos com 80 anos ou mais da coorte do Projeto Veranópolis foi selecionada para genotipagem da APOE. Na linha de base, foram coletadas variáveis antropométricas, dosagens sanguíneas de glicose e lipídeos, pressão arterial e variáveis de estilo de vida (tabagismo, consumo de álcool e atividade física). A escala Bayer de Atividades da Vida Diária foi aplicada aos cuidadores dos idosos. O tempo de seguimento total do estudo foi 21 anos. Um p<0,05 bicaudal foi considerado estatisticamente significativo. Resultados: Não encontramos associação entre os genótipos da APOE e mortalidade. Entretanto, o risco de morte em idosos fumantes foi 2,30 vezes (hazard ratio [HR]; intervalo de confiança de 95% [IC 95%] 1,01 a 5,24); em diabéticos, 3,95 vezes (HR; IC 95% 1,27 a 12,30) do risco dos não diabéticos. Indivíduos que praticavam atividade física vigorosa tiveram uma redução no risco de óbito em 51% (HR = 0,49; IC 95% 0,27 a 0,88). Para o aumento de 1 mmHg na pressão arterial sistólica houve uma redução de 2% (HR = 0,98; IC 95% 0,97 a 0,99) no risco de morte. Conclusão: Nesta amostra de longevos, não houve associação entre os genótipos da APOE e mortalidade. Entretanto, os fatores de risco cardiovasculares clássicos podem ser importantes para a mortalidade geral em pessoas muito idosas.

Abstract Background: Knowledge of environmental and genetic factors for healthy aging in elderly people is controversial. In addition to this evidence, few studies have been designed for this population. Objectives: To investigate the relationship between the most frequent apolipoprotein E (APOE) genotypes and mortality in very elderly individuals living in a community and to evaluate survival according to cardiovascular risk factors. Methods: A sample of 74 elderly individuals aged ≥ 80 years, from the Veranópolis Project cohort, was selected for APOE genotyping. At baseline, anthropometric variables, glucose and lipid levels, blood pressure, and lifestyle variables (smoking, alcohol consumption, and physical activity) were collected. The Bayer Activities of Daily Living Scale was applied to their caregivers. Total study follow-up was 21 years. Two-sided p < 0.05 was considered statistically significant. Results: There was no association between APOE genotypes and mortality. However, the risk of death in elderly smokers was 2.30 times higher (hazard ratio [HR], 95% CI 1.01 to 5.24); in individuals with diabetes, it was 3.95 times higher (HR, 95% CI 1.27 to 12.30) than in individuals without diabetes. Subjects who practiced vigorous physical activity had a 51% reduction in risk of death (HR = 0.49, 95% CI 0.27 to 0.88). For an increase of 1 mmHg in systolic blood pressure, there was a 2% reduction (HR = 0.98, 95% CI 0.97 to 0.99) in risk of death. Conclusion: In this sample population, APOE genotypes were not associated with mortality. However, classic cardiovascular risk factors may be important for overall mortality in the very elderly.

Humans , Aged , Aged, 80 and over , Cardiovascular Diseases/genetics , Apolipoproteins E , Activities of Daily Living , Risk Factors , Cohort Studies
Acta méd. colomb ; 45(2): 22-29, Jan.-June 2020. tab
Article in English | LILACS, COLNAL | ID: biblio-1130687


Introduction: Alzheimer's dementia (AD) has an early and a late onset. More information is needed regarding risk factors according to the age of onset of AD. The objective is to characterize the sociodemographic, anthropometric, laboratory and genetic variables as well as the history of patients with ade novodiagnosis of AD, by age of onset, at the Hospital Universitario C.A.R.I.'s mental health site over a period of two years. Methods: a cross-sectional descriptive study of 39 patients with ade novodiagnosis of AD. A questionnaire was completed, paraclinical studies were ordered and a blood sample was obtained for APOE genotyping. The IBM SPSS 21 software was used for analysis. Results: 82.05% had late-onset and 17.95% had early-onset AD. Of those with early-onset AD, 57.14% were females, as were 71.90% of those with late-onset AD. 71.44% of those with early-onset AD were married and 53.12% with late-onset AD were widowed. Only 14.29% with early-onset and 18.75% with late-onset AD had optimal LDL levels. Altogether, 79.49% of the population was heterozygous for the ε4 allele. 71.43% of those with early-onset AD had a family history of dementia. Discussion: age is the main factor associated with AD and females were more frequent in both groups. Social relationships play a role in early detection of symptoms. Lipid profile abnormalities were seen in both groups. Having at least one ε4 allele is a frequent finding in AD. Having a first-degree relative with dementia and/or Alzheimer's was more frequent in early-onset AD.(Acta Med Colomb 2020; 45. DOI:

Introducción: la demencia de tipo Alzheimer (DTA) tiene presentación precoz o tardía. Es necesaria mayor información sobre factores de riesgo según edad de aparición de DTA. El objetivo es caracterizar variables sociodemográficas, antropométricas, de laboratorio, genéticas y antecedentes en pacientes con diagnósticode novode DTA según edad de aparición en el Hospital Universitario C.A.R.I. sede salud mental en un periodo de dos años. Metodología: estudio descriptivo transversal con 39 pacientes con diagnósticode novode DTA. Se realizó un cuestionario, solicitaron paraclínicos y se obtuvo una muestra sanguínea para genotipificación deAPOE.Se utilizó el software IBM SPSS 21 para análisis. Resultados: el 82.05% tenían DTA tardío y 17.95% DTA precoz. El 57.14% con DTA precoz y 71.90% con DTA tardía eran de sexo femenino. El 71.44% con DTA precoz eran casados y 53.12% con DTA tardío eran viudos. Solo 14.29% con DTA precoz y 18.75% con DTA tardío tenían niveles óptimos de LDL. El 79.49% de la población era heterocigoto para el alelo ε4. El 71.43% con DTA precoz tenía antecedente familiar de demencia. Discusión: la edad es el principal factor asociado a DTA y el sexo femenino fue más frecuente en ambos grupos. Las relaciones sociales juegan un rol en la identificación temprana de la sintomatología. Las alteraciones del perfil lipídico se evidenciaron en ambos grupos. Tener al menos un alelo ε4 es un hallazgo frecuente de DTA. Tener un familiar con demencia y/o Alzheimer de primer grado de consanguinidad fue más frecuente en DTA precoz.(Acta Med Colomb 2020; 45. DOI:

Humans , Male , Female , Adult , Alzheimer Disease , Apolipoproteins E , Schizophrenia , Dementia
Arch. cardiol. Méx ; 90(2): 130-136, Apr.-Jun. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131021


Abstract Objective: Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score > 8 points qualifies the patient as "definite" for FH diagnosis. The detection of the presence of a variant in these genes allows carrying out familial cascade screening and better characterizes the patient in terms of prognosis and treatment. Methods: In the context of the FH detection program in Argentina (Da Vinci Study) 246 hypercholesterolemic patients were evaluated, 21 with DLCN score > 8 (definite diagnosis).These patients were studied with next generation sequencing to detect genetic variants, with an extended panel of 23 genes; also they were adding the large rearrangements analysis and a polygenic score of 10 SNP (single nucleotide polymorphism) related to the increase in LDL-c. Results: Of the 21 patients, 10 had variants in LDLR, 1 in APOB with APOE, 1 in LIPC plus elevated polygenic score, and 2 patients showed one deletion and one duplication in LDLR, the later with a variation in LIPA. It is highlighted that 6 of the 21 patients with a score > 8 did not show any genetic alteration. Conclusions: We can conclude that 28% of the patients with definite clinical diagnosis of FH did not show genetic alteration. The possible explanations for this result would be the presence of mutations in new genes, confusing effects of the environment over the genes, the gene-gene interactions, and finally the impossibility of detecting variants with the current available methods.

Resumen Objetivo: La hipercolesterolemia familiar (HF) es una enfermedad monogénica asociada a variantes en los genes RLDL, APOB y PCSK9. El diagnóstico inicial se basa en criterios clínicos, como el de la red de clínica de lípidos holandesa (DLCN). Un puntaje > 8 puntos califica al paciente como "definitivo" para diagnóstico de HF. La identificación de una variante en estos genes permite realizar el cribado en cascada familiar y caracterizar mejor al paciente en cuanto al pronóstico y el tratamiento. Métodos: En el marco del Programa de Detección de HF en Argentina (Estudio Da Vinci) se evaluó a 246 pacientes hipercolesterolémicos, 21 con puntaje DLCN > 8 (diagnóstico definitivo). Se estudió a estos pacientes con secuenciación de próxima generación para reconocer variantes genéticas, con un panel ampliado de 23 genes, sumado al análisis de grandes rearreglos y por último se aplicó un score poligénico de 10 SNP (polimorfismo de nucleótido único) relacionados con aumento del c-LDL. Resultados: De los 21 pacientes, 10 presentaron variantes en RLDL, uno en APOB junto a APOE, uno en LIPC más puntaje poligénico elevado, dos pacientes con una deleción y una duplicación en RLDL y este último caso con una variante en LIPA. Es destacable que 6 de los 21 pacientes con puntaje DLCN > 8 no mostraron ninguna alteración genética. Conclusiones: El 28% de los pacientes con diagnóstico clínico definitivo de HF no evidenció alteración genética. Las posibles explicaciones de este resultado serían la presencia de mutaciones en nuevos genes, los efectos confundidores del ambiente sobre los genes o la interacción gen-gen y por último la imposibilidad de detectar variantes con la metodología actual disponible.

Humans , Male , Female , Adult , Middle Aged , Aged , Receptors, LDL/genetics , Apolipoprotein B-100/genetics , Proprotein Convertase 9/genetics , Hyperlipoproteinemia Type II/genetics , Apolipoproteins E/genetics , Phenotype , Argentina , Genetic Variation , Polymorphism, Single Nucleotide , Mutation
J. bras. nefrol ; 41(3): 393-399, July-Sept. 2019. graf
Article in English | LILACS | ID: biblio-1040251


Abstract Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.

Resumo A glomerulopatia por lipoproteínas (GLP) é uma patologia rara que causa síndrome nefrótica e/ou insuficiência renal. Na microscopia, a GLP é caracterizada pela presença de trombos de lipoproteínas em capilares glomerulares dilatados devido a diferentes mutações no gene da ApoE. O gene da ApoE está localizado no cromossomo 19q13.2 e pode ser identificado em quase todas as lipoproteínas séricas. A ApoE age como fator de proteção na arterioesclerose por conta de sua interação com a depuração de lipoproteínas mediada por receptores e com o receptor de colesterol. Dentre os polimorfismos mais comuns destacam-se ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3 e ApoE4/4. A GLP pode acometer indivíduos de todas as faixas etárias, com discreta predominância do sexo masculino. Pacientes afetados tipicamente apresentam dislipidemia, hiperlipoproteinemia tipo III e proteinúria. O tratamento da GLP é conduzido com fenofibrato, antilipêmicos, corticosteroides, LDL-aferese, troca de plasma, antiplaquetários, anticoagulantes, uroquinase e transplante renal. Recidiva no enxerto renal indica a existência de componentes patogênicos do complexo humoral extraglomerular resultante de metabolismo lipoproteico anômalo, possivelmente associado a ApoE.

Humans , Male , Female , Child, Preschool , Adult , Middle Aged , Kidney Diseases/pathology , Kidney Diseases/therapy , Apolipoproteins E/genetics , Sex Factors , Kidney Transplantation , Treatment Outcome , Kidney Diseases/complications , Kidney Diseases/genetics , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/etiology , Mutation , Hypolipidemic Agents/therapeutic use
Article in Chinese | WPRIM | ID: wpr-776564


OBJECTIVE@#To evaluate the effects of 12 weeks high intensity interval training(HIIT) on serum lipids profile in patients with dyslipidemia of different apolipoprotein E(ApoE) genotypes.@*METHODS@#Eighty-eight patients with dyslipidemia were screened by fasting blood lipid as subjects. Apolipoprotein E genotypes were detected in oral mucosa of subjects. Serum lipids before and after 12 weeks high intensity interval training were measured to analysis the effect of high intensity interval training on serum lipids.@*RESULTS@#Five genotypes were detected in 88 cases of dyslipidemia. The distributions were ApoE3/3>ApoE3/4>ApoE2/3>ApoE2/2>ApoE2/4,and allele ε3>ε2=ε4. Before exercise intervention, the level of total cholesterol in patients with ε4 allele was significant higher than those in patients with ε2 and ε3 (P<0.01), low density lipoprotein cholesterol in patients with ε4 was significant higher than that of patients with ε2 (P<0.05), and the other indexes had no significant difference among the groups (P> 0.05). After 12 weeks high intensity interval training, the levels of total cholesterol, triglyceride and low density lipoprotein cholesterol were decreased significantly ,while the level of high density lipoprotein cholesterol was increased in those patients with ε3 genotype. For those individuals with ε4 genotype , their serum levels of total cholesterol and low density lipoprotein cholesterol were reduced after 12 weeks high intensity interval training , but there was no changes in serum levels of triglyceride and high density lipoprotein cholesterol. For those individuals with ε2 genotype, there was no significant improvement in serum lipids after 12 weeks high intensity interval training interventions.@*CONCLUSION@#The polymorphisms of apolipoprotein E gene resulted in different effects of exercise interventions on serum lipids of dyslipidemia. Twelve weeks high intensity interval training can be used as an intervention method to regulate serum lipids of dyslipidemia with ε3 and ε4 alleles.

Apolipoproteins E , Genetics , Dyslipidemias , Genetics , Therapeutics , Genotype , High-Intensity Interval Training , Humans , Lipids , Blood
Article in English | WPRIM | ID: wpr-765095


BACKGROUND: Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study. METHODS: This study population included participants from the Dong-gu and Namwon Studies. APOE genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference. RESULTS: In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97–1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74–0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97–1.20) and 0.80 (95% CI, 0.70–0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52–0.92) for the E2 allele and 1.25 (95% CI, 1.03–1.53) for the E4 allele. CONCLUSION: In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans.

Alleles , Apolipoproteins E , Apolipoproteins , Asian Continental Ancestry Group , Cardiovascular Diseases , Cohort Studies , Ethnic Groups , Genotype , Humans , Life Style , Mortality , Negotiating , Proportional Hazards Models
Article in English | WPRIM | ID: wpr-740300


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
Arq. neuropsiquiatr ; 76(4): 241-246, Apr. 2018. tab
Article in English | LILACS | ID: biblio-888385


ABSTRACT Objective: The objective of this study was to characterize the conventional lipid profile, oxLDL levels and ApoE polymorphism in patients with Alzheimer's disease (AD) and in elderly individuals without cognitive impairment. Methods: Eighty elderly individuals were selected and the levels of oxLDL were determined using the ELISA kit, and ApoE gene polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism. Results: Significantly reduced levels of oxLDL were observed in patients with AD compared to the control group. A higher frequency of the ApoE ε4 allele was observed in patients with AD compared to controls. No difference was observed for total cholesterol, HDL-C, and LDL-C levels between the two groups, while triglyceride levels were higher in controls compared with patients with AD. Conclusion: The data analyzed together did not reveal significant differences in lipid profiles, including oxLDL levels. However, the importance of lipid changes in the genesis of the disease cannot be ruled out. Nevertheless, the ApoE ε4 allele was significantly more frequent in patients with Alzheimer's dementia in agreement with previous findings in the literature, but this genetic component did not change the levels of oxLDL.

RESUMO Objetivo: O objetivo deste estudo foi caracterizar o perfil lipídico convencional, os níveis de LDL-ox e o polimorfismo da ApoE em pacientes com doença de Alzheimer (DA) e em indivíduos idosos sem comprometimento cognitivo. Métodos: Foram selecionados oitenta indivíduos idosos. Os níveis de LDL-ox foram determinados usando o kit ELISA e a investigação do polimorfismo do gene da ApoE por PCR-RFLP. Resultados: Níveis significativamente reduzidos de LDL-ox foram observados em pacientes com DA comparado ao grupo controle. Uma maior frequência do alelo ε4 da ApoE foi observada nos pacientes com DA em relação aos controles. Nenhuma diferença foi observada para os níveis de colesterol total, HDL-C e LDL-C entre os dois grupos, enquanto níveis de triglicérides foram mais altos em controles comparados aos pacientes com DA. Conclusão: Os dados analisados em conjunto não revelaram diferenças significativas no perfil lipídico, incluindo os níveis de LDL-ox. No entanto, não se pode excluir a importância de alterações lipídicas na gênese da doença. Não obstante, o alelo ε4 da ApoE foi signicativamente mais frequente nos pacientes com demência de Alzheimer em concordância com achados prévios da literatura, mas esse componente genético não interferiu nos níveis de LDL-ox.

Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Apolipoproteins E/genetics , Polymorphism, Genetic/genetics , Alzheimer Disease/blood , Lipoproteins, LDL/blood , Polymorphism, Restriction Fragment Length , Enzyme-Linked Immunosorbent Assay , Case-Control Studies , Polymerase Chain Reaction , Alzheimer Disease/genetics , Lipids/blood
Rev. Hosp. Ital. B. Aires (2004) ; 38(1): 5-10, mar. 2018. tab.
Article in English | LILACS | ID: biblio-1023455


The dysfunction in the serotoninergic neurotransmission has been classically associated with major depressive disorder (MDD); however, other pathways and processes seem to have a role in this illness, such as neurogenesis and related molecules: the Brain-Derived Neurotrophic Factor (BDNF) and the Apolipoprotein E (APOE). There are many reports that indicate an association between certain polymorphism in these genes and MDD. The aim of our study was to analyze the possible association between MDD and polymorphisms in HTR2A (5-hydroxytryptamine receptor 2A), BDNF and APOE genes in a sample of the Argentinean population previously studied for 2 polymorphisms in SLC6A4 (Solute Carrier Family 6 Member 4) gene. Five polymorphisms were studied (rs6311 and rs6313 in HTR2A; rs429358 and rs7412 in APOE, and rs6265 in BDNF) in 95 MDD patients and 107 non-related controls. No statistically significant differences were observed between groups when analyzing the association with a single marker using logistic regression; however, when a possible combinatory effect of the polymorphisms (including previously studied polymorphisms in SLC6A4 gene) was analyzed using a dominant model for the risk alleles, the genotypes L/S_10/12_G/A (OR=3.57(95%CI=1.43-8.93); p=0.004, adjusted p-value=0.01) in SLC6A4 and BDNF genes and L/S_10/12_T/C_3/3_G/A in SLC6A4, HTR2A, APOE and BDNF genes (OR=5.99(95%CI=1.66-21.56); p=0.002, adjusted p-value=0.07), were more prevalent in patients than in controls (20%vs.6% and 15%vs.3%, respectively). Even though it is necessary to replicate these findings in a larger population, our results suggest a possible interaction between molecules involved in neurogenesis (BDNF and APOE), serotoninergic neurotransmission (SLC6A4 and HTR2A) and the pathogenesis of MDD. (AU)

La disfunción en la neurotransmisión serotoninérgica ha sido clásicamente asociada con el trastorno depresivo mayor (TDM); sin embargo, otras vías y procesos parecerían tener un rol en esta enfermedad, como la neurogénesis y moléculas asociadas: el factor neurotrófico derivado del cerebro (BDNF) y la apoliproteína E (APOE). Existen reportes en los que se establecen asociaciones entre polimorfismos en estos genes y el TDM. El objetivo de nuestro trabajo fue analizar la posible asociación entre el TDM y polimorfismos en los genes HTR2A (receptor 5-hidroxitriptamina 2A), BDNF y APOE en una muestra de la población argentina previamente estudiada para 2 polimorfismos en el gen SLC6A4 (transportador soluble familia 6 miembro 4). Se estudiaron 5 polimorfismos (rs6311 y rs6313 en HTR2A; rs429358 y rs7412 en APOE; rs6265 en BDNF) en 95 pacientes con TDM y 107 controles no relacionados. No se observaron diferencias significativas entre grupos al analizar la asociación por regresión logística con un único marcador; cuando se analizó el posible efecto combinatorio de polimorfismos (incluyendo los previamente estudiados para el gen SCL6A4) usando un modelo dominante para los alelos de riesgo, los genotipos L/S_10/12_G/A (OR=3,57(95%CI=1,43-8,93); p=0,004, valor-p-ajustado=0,01) en SLC6A4 y BDNF y L/S_10/12_T/C_3/3_G/A en SLC6A4, HTR2A, APOE y BDNF (OR=5,99(95%CI=1,66-21,56); p=0,002, valor-p-ajustado=0,07), fueron más prevalentes en pacientes que controles (20%vs.6% y 15%vs.3% respectivamente). Si bien es necesario replicar estos hallazgos en una población más grande, nuestros resultados sugieren una posible interacción entre moléculas involucradas en la neurogénesis (BDNF y APOE), la neurotransmisión serotoninérgica (SLC6A4 y HTR2A) y la patogenia de la depresión mayor. (AU)

Humans , Male , Female , Adult , Middle Aged , Young Adult , Apolipoproteins E/deficiency , Polymorphism, Genetic , Brain-Derived Neurotrophic Factor/deficiency , Receptors, Serotonin, 5-HT2/deficiency , Depressive Disorder, Major/genetics , Serotonin Plasma Membrane Transport Proteins/deficiency , Apolipoproteins E/genetics , Argentina/epidemiology , Brain-Derived Neurotrophic Factor/genetics , Receptors, Serotonin, 5-HT2/genetics , Depressive Disorder, Major/pathology , Serotonin Plasma Membrane Transport Proteins/genetics
Article in English | WPRIM | ID: wpr-718822


Alzheimer's disease (AD) related genes have been elucidated by advanced genetic techniques. Familial autosomal dominant AD genes founded by linkage analyses are APP, PSEN1, PSEN2, ABCA7, and SORL1. Genome-wide association studies have found risk genes such as ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-HLA-DRB1, INPP5D, MEF2C, MS4A6A/MS4A4E, NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1. ABCA7, SORL1, TREM2, and APOE are proved to have high odds ratio (>2) in risk of AD using next generation sequencing studies. Thanks to the promising genetic techniques such as CRISPR-CAS9 and single-cell RNA sequencing opened a new era in genetics. CRISPR-CAS9 can directly link genetic knowledge to future treatment. Single-cell RNA sequencing are providing useful information on cell biology and pathogenesis of diverse diseases.

Alzheimer Disease , Apolipoproteins E , CRISPR-Cas Systems , Genetic Techniques , Genetics , Genome-Wide Association Study , Odds Ratio , Sequence Analysis, RNA , Single-Cell Analysis
Yonsei Medical Journal ; : 801-805, 2018.
Article in English | WPRIM | ID: wpr-716421


Cerebral amyloid angiopathy (CAA) is associated with perivascular disruption, which is caused by progressive amyloid-beta (Aβ) deposition in vessels. Previous autopsy studies have shown that the prevalence of CAA in Alzheimer's disease (AD) is 70% to 90%. CAA is principally characterized by restricted lobar microbleeds (MBs), which can be detected by gradient-echo T2* (GRE) and susceptibility-weighted imaging (SWI). We herein report on a 62-year-old man who presented with 8 years of memory impairment. The apolipoprotein E (APOE) genotype was ε4/ε4, and a brain GRE performed 28 months before death revealed mild atrophy and no MBs. At autopsy, the patient scored “A3, B3, C3” according to the National Institute on Aging-Alzheimer's Association guidelines; the patient thus exhibited a high level of AD neuropathological changes. Furthermore, immunohistochemical staining for Aβ showed antibody accumulation and severe cerebral amyloid angiopathic changes in numerous vessels with amyloid deposits. Our case suggests that radiological CAA markers, such as cerebral microbleed (CMB) or cerebral superficial siderosis, may not suffice to detect amyloid angiopathy in cerebral vessels. CAA should therefore be considered as a combined pathology in APOE ε4 homozygotes with AD, even if such patients do not exhibit CMB on MRI.

Alzheimer Disease , Amyloid , Apolipoproteins , Apolipoproteins E , Atrophy , Autopsy , Brain , Cerebral Amyloid Angiopathy , Genotype , Homozygote , Humans , Magnetic Resonance Imaging , Memory , Middle Aged , Pathology , Plaque, Amyloid , Prevalence , Siderosis
Gut and Liver ; : 201-207, 2018.
Article in English | WPRIM | ID: wpr-713230


BACKGROUND/AIMS: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. METHODS: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). RESULTS: Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. CONCLUSIONS: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.

Apolipoprotein A-I , Apolipoprotein A-II , Apolipoprotein C-II , Apolipoprotein C-III , Apolipoproteins , Apolipoproteins B , Apolipoproteins E , Cholesterol , Genotype , Hepacivirus , Hepatitis C , Hepatitis , Humans , Lipid Metabolism , Lipoproteins , Recurrence
Article in Chinese | WPRIM | ID: wpr-776584


OBJECTIVE@#To observe the changes of apolipoprotein E (apoE) protein expression of pulmonary tissue in mice with pulmonary hypertension induced by hypoxia.@*METHODS@#The animal model of hypoxic pulmonary hypertension was established by exposing the mice to isobaric hypoxic chamber for 3 weeks (23 h/d, regular chow feed).Twenty male wild type (WT) C57BL/6 mice and twenty apoE gene knockout (apoE-KO) mice were randomly divided into normoxia group and hypoxia group. The plasma concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were detected by ELISA method. The protein expression of apoE in lung and liver, and peroxisome proliferators-activated receptor gamma (PPARγ) in lung were measured by Western blot.@*RESULTS@#①In WT mice, the right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 68% and 59% (<0.05), respectively. The plasma concentration of HDL and HDL/LDL of hypoxia group were significantly lower than those of normoxia group by 17% and 40% (<0.05), respectively.The protein expression of apoE in lung and in liver of hypoxia group were significantly down-regulated than those of normoxia group by 48% and 52% (<0.05), respectively.The protein expression of PPARγ in lung was significantly down-regulated than that of normoxia group by 37%(<0.05).RVSP were significantly negative correlated with the protein levels of apoE and PPARγ in lung (<0.01).② In apoE-KO mice, RVSP and the weight ratio of RV to LV+S of hypoxia group were significantly higher than those of normoxia group by 96% and 86% (<0.05), respectively.RVSP and RV to (LV+S) of hypoxia group in apoE-KO mice were significantly higher than those of hypoxia group in WT mice by 29% and 24% (<0.05), respectively.@*CONCLUSIONS@#Down-regulated expression of apoE in lung tissue participates in the pathological proceeding of pulmonary hypertension induced by hypoxia.

Animals , Apolipoproteins E , Hypertension, Pulmonary , Hypoxia , Lung , Male , Mice , Mice, Inbred C57BL