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Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice

BECKER, Luis E.; KOLEGANOVA, Nadezda; PIECHA, Grzegorz; NORONHA, Irene L.; ZEIER, Martin; GELDYYEV, Aman; KOEKENY, Gabor; RITZ, Eberhard; GROSS, Marie-Luise
Fonte: AMER PHYSIOLOGICAL SOC Publicador: AMER PHYSIOLOGICAL SOC
Tipo: Artigo de Revista Científica
ENG
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Becker LE, Koleganova N, Piecha G, Noronha IL, Zeier M, Geldyyev A, Kokeny G, Ritz E, Gross ML. Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice. Am J Physiol Renal Physiol 300: F772-F782, 2011. First published December 15, 2010; doi:10.1152/ajprenal.00042.2010.-Despitean only minor reduction in the glomerular filtration rate, uninephrectomy (UNX) markedly accelerates the rate of growth of atherosclerotic plaques in ApoE-/- mice. It has been suggested that vitamin D receptor (VDR) activation exerts an antiproliferative effect on vascular smooth muscle cells, but the side effects may limit its use. To assess a potentially different spectrum of actions, we compared the effects of paricalcitol and calcitriol on remodeling and calcification of the aortic wall in sham-operated and UNX ApoE-/- mice on a diet with normal cholesterol content. Sham-operated and UNX mice were randomly allotted to treatment with solvent, calcitriol (0.03 mu g/kg) or paricalcitol (0.1 mu g/kg) 5 times/wk intraperitoneally for 10 wk. Semithin (0.6 mu m) sections of the aorta were analyzed by 1) morphometry, 2) immunohistochemistry, and 3) Western blotting of key proteins involved in vascular calcification and growth. Compared with sham-operated animals (5.6 +/- 0.24)...

Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women

Issa, Mustafa H.; Cerda, Alvaro; Genvigir, Fabiana Dalla Vecchia; Cavalli, Selma A.; Bertolami, Marcelo C.; Faludi, Andre A.; Hirata, Mario Hiroyuki; Hirata, Rosario Dominguez Crespo
Fonte: PERGAMON-ELSEVIER SCIENCE LTD; OXFORD Publicador: PERGAMON-ELSEVIER SCIENCE LTD; OXFORD
Tipo: Artigo de Revista Científica
ENG
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Menopause is associated with changes in lipid levels resulting in increased risk of atherosclerosis and cardiovascular events. Hormone therapy (HT) and atorvastatin have been used to improve lipid profile in postmenopausal women. Effects of HT, atorvastatin and APOE polymorphisms on serum lipids and APOE and LXRA expression were evaluated in 87 hypercholesterolemic postmenopausal women, randomly selected for treatment with atorvastatin (AT, n=17), estrogen or estrogen plus progestagen (HT, n=34) and estrogen or estrogen plus progestagen associated with atorvastatin (HT+AT, n=36). RNA was extracted from peripheral blood mononuclear cells (PBMC) and mRNA expression was measured by TaqMan (R) PCR. APOE epsilon 2/epsilon 3/epsilon 4 genotyping was performed using PCR-RFLP. Total cholesterol (TC). LDL-c and apoB were reduced after each treatment (p<0.001). Triglycerides, VLDL-c and apoAl were reduced only after atorvastatin (p<0.05), whereas triglycerides and VLDL-c were increased after HT (p=0.01). HT women had lower reduction on TC, LDL-c and apoB than AT and HT+AT groups (p<0.05). APOE mRNA expression was reduced after atorvastatin treatment (p=0.03). Although LXRA gene expression was not modified by atorvastatin, it was correlated with APOE mRNA before and after treatments. Basal APOE mRNA expression was not influenced by gene polymorphisms...

Associação entre infecção experimental por Mycoplasma pneumoniae e/ou Chlamydophila (Chlamydia) pneumoniae e a intensidade das lesões ateroscleróticas da aorta, em camundongos C57BL/6 apoE KO, com ênfase na diferença entre os sexos; Association between experimental infection by Mycoplasma pneumoniae and/or Chlamydophila (Chlamydia) pneumoniae and intensity of atherosclerotic lesions in the aorta of C57BL/6 apoE KO mice, with emphasis on the difference between sexes

Damy, Sueli Blanes
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 03/07/2006 PT
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Os mecanismos pelos quais os agentes infecciosos, independentes ou não de meio ambiente permissivo, podem promover a aterogênese e as manifestações clínicas não estão completamente esclarecidos. Apesar das numerosas publicações demonstrando a presença de antígenos ou DNA de agentes infecciosos nas placas de ateroma, a questão se o agente infeccioso pode iniciar o processo aterosclerótico ou agravá-lo permanece sem resposta, possibilitando o aprofundamento das pesquisas neste assunto. Desta forma, este trabalho tem como objetivo estudar se a infecção experimental, por C.pneumoniae e/ou M.pneumoniae, em camundongos C57BL/6 apoE KO induziria ou afetaria a intensidade e a característica de vulnerabilidade da placa ateromatosa, de acordo com o sexo e/ou a dieta rica em colesterol. Métodos: um grupo de camundongos recebeu dieta enriquecida com 1% de colesterol (hiperlipidêmica), e o outro ração com formulação adequada para espécie (normolipidêmica), desde os dois meses de idade. Aos 8 meses de idade foram subdivididos, inoculados com 106 UFI de C.pneumoniae e/ou 106 UFC de M.pneumoniae, por via intraperitoneal, reinoculados um mês após e sacrificados aos 10 meses de idade. Para análise histopatológica secções transversais das aortas torácicas foram processadas para emblocamento em parafina...

Análise da presença de mutação no gene TARDBP em pacientes com degeneração lobar frontotemporal e implementação de metodologia para determinação dos polimorfismos do gene APOE em pacientes com Doença de Alzheimer em São Paulo - SP; Analysis of the presence of mutation in TARDBP gene in patients with frontotemporal lobar degeneration and implementation of APOE gene methodology for polymorphism determination in patients with Alzheimer's disease in São Paulo - SP

Costa, Thaís Virgínia Moura Machado
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 15/08/2012 PT
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Atualmente, as demências tornam-se mais prevalentes e constituem-se como um importante problema de saúde pública mundial. A Degeneração Lobar Frontotemporal (DLFT) e a Doença de Alzheimer (DA) são as de maior incidência. A investigação dos fatores de risco para as demências degenerativas inscreve-se entre os temas mais relevantes das neurociências e a avaliação dos fatores de risco de natureza genética tem produzido contribuições importantes. Na DLFT, mutações no gene TARDBP, codificador da proteína nuclear TDP-43, estão entre as ocorrências genéticas mais descritas, enquanto que para a DA, o alelo 4 do gene da apolipoproteína E (APOE) é o principal fator de risco. Pacientes com diagnóstico clínico de DLFT (n=47) e de DA provável (n=30) recebidos do ambulatório do Grupo de Neurologia Cognitiva e do Comportamento (GNCC) da Clínica Neurológica do HC-FMUSP foram convidados a participar do estudo. Amostras de sangue foram coletadas para a realização da extração de DNA linfocitário. Os éxons de 1-6 do gene TARDBP foram amplificados por PCR e seus produtos foram sequenciados em sequenciador automático. Os polimorfismos do gene APOE foram determinados através da técnica de PCR em tempo real. A análise do gene da TDP-43 em pacientes com DLFT mostrou a presença de uma mutação na região do éxon 6 do TARDBP (g.14935A>G) em um paciente do sexo masculino...

Relationship of the APOE polymorphism and lipid profile: A population-based study in the Azores Islands (Portugal)

Raposo, Mafalda; Dahmani, Yahya; Silva, Francisca; Tavares, M.; Cymbron, Teresa; Santos, Cristina; Bettencourt, Conceição; Ferin, Rita; Correia, Cristina; Pavão, Maria Leonor; Lima, Manuela
Fonte: Universidade dos Açores Publicador: Universidade dos Açores
Tipo: Conferência ou Objeto de Conferência
Publicado em /05/2009 ENG
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European Human Genetics Conference 2009: Abstract P17.18 em Livro de Resumos. Austria Center Vienna, Vienna, Austria, Saturday, May 23 – Tuesday, May 26, 2009.; The factors leading to a two-fold mortality rate from coronary artery disease (CAD) in the Azores, as compared to Mainland Portugal, have not been elucidated. Previous studies reported a population tendency for hypercholesterolemia, one of the main factors contributing to the development of atherosclerosis (AT), considered the primary cause of CAD. Apolipoprotein E has a key role in plasma lipid metabolism, given its function as a ligand for cell-surface receptor mediated uptake of lipoproteins. Polymorphism in the apolipoprotein gene (APOE) results in three major isoforms encoded by three codominant alleles (E2, E3 and E4). With the purpose of establishing the pattern of variation at the APOE locus and determining its association with lipid profile, we studied a random sample of 298 unrelated, apparently healthy individuals of Azorean origin. In nearly 50% of the sample total cholesterol (TC) was above 200mg/dl; in 25% of the individuals LDL-cholesterol (LDL-C) was higher than 130 mg/dl. Allele frequencies were 0.0833, 0.8317 and 0.0850 for E2, E3 and E4, respectively. Genotype frequencies were higher for E3*E3 genotype (66.1%); genotype distribution displayed conformity with Hardy-Weinberg expectations. No differences in allelic frequencies were found in comparison with other Caucasian populations...

Polymorphism of the ApoE locus in the Azores Islands (Portugal)

Bettencourt, Conceição; Montiel, Rafael; Santos, Cristina; Pavão, Maria Leonor; Viegas-Crespo, Ana Maria; Lopes, Paula Alexandra; Lima, Manuela
Fonte: nature publishing group Publicador: nature publishing group
Tipo: Conferência ou Objeto de Conferência
Publicado em //2006 ENG
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Abstract de Comunicação em painel (P1088) apresentada em "European Human Genetics Conference 2006", 6-9 de Maio de 2006, Amsterdão, Holanda.; The aim of this work was to report on the polymorphism of the ApoE locus in the Azores Islands (Portugal) in order to get insights on the genetic background that influences the lipid profile in this population, ascertained as considerably high in a preliminary study of a sample of healthy subjects (60% of individuals were hypercholesterolemics). One hundred and twenty six Azorean individuals were typed for ApoE polymorphism using standard PCR-RFLP. The allelic frequencies obtained for ε2, ε3 and ε4 were 6.75%, 83.73% and 9.52%, respectively. Genotypic frequencies were in conformity with Hardy-Weinberg expectations. The ε3/ε3 genotype presented the highest frequency (69.84%), whilst ε4/ε4 was the least frequent (0.79%). The genotypic and allelic frequencies observed were similar to those reported for other Iberian samples. Furthermore, Nei’s gene diversity (0.2864±0.0351) was similar to the reported for samples from Mainland Portugal. Results obtained did not evidence a particular behaviour of the ApoE locus that could be directly related with the high levels of total cholesterol determined in the Azorean population.

Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients

Errera,F.I.V.; Silva,M.E.R.; Yeh,E.; Maranduba,C.M.C.; Folco,B.; Takahashi,W.; Pereira,A.C.; Krieger,J.E.; Passos-Bueno,M.R.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2006 EN
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Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and epsilon2/epsilon3/epsilon4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (epsilon2, epsilon3 and epsilon4 in cases: 9...

Protective effect of the APOE-e3 allele in Alzheimer’s disease

de-Almada,B.V.P.; de-Almeida,L.D.; Camporez,D.; de-Moraes,M.V.D.; Morelato,R.L.; Perrone,A.M.S.; Belcavello,L.; Louro,I.D.; de-Paula,F.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2012 EN
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Although several alleles of susceptibility to Alzheimer’s disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95%CI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46...

Incidence of dementia and association with APOE genotype in older Cubans

Rodríguez,Juan J. Llibre; Cepero,Adolfo Valhuerdi; Gil,Isis Y. Sanchez; Medina,Ana M. López; Llibre-Guerra,Juan C.; Llibre-Guerra,Jorge J.; Teruel,Beatriz Marcheco; Ferri,Cleusa P.; Prince,Martin
Fonte: Associação de Neurologia Cognitiva e do Comportamento Publicador: Associação de Neurologia Cognitiva e do Comportamento
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2014 EN
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OBJECTIVE: In an admixed population of older Cubans, the incidence and association of APOE and socio demographic risk factors with dementia incidence was estimated. METHODS: A single-phase survey (baseline) of all over 65-year-olds residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and associations with sociodemographic risk factors of the APOE ε4 genotype. RESULTS: The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95% CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6-23.5). Older age, a family history of dementia and APOE ε4 genotype were independent risk factors for incident 10/66 dementia. APOE genotype was associated cross-sectionally with dementia prevalence, but the effect on the incidence of dementia was attenuated, and only apparent among those in the youngest age group. CONCLUSION: The incidence of dementia in the older Cuban population is relatively high and similar to levels reported in Europe and North-America. The study showed that the relationship between APOE ε4 and incident dementia is stronger in the younger-old than the older-old and that this change must be taken into account in models of dementia.

Polimorfismos dos genes CYP 46 e APOE e declínio cognitivo em idosos residentes no distrito de Fernando de Noronha-PE

Nusya de Medeiros Garcia, Analia; Ataíde Júnior, Luiz (Orientador)
Fonte: Universidade Federal de Pernambuco Publicador: Universidade Federal de Pernambuco
Tipo: Outros
PT_BR
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O Declínio Cognitivo Leve (DCL) é um estado mental considerado a zona de transição entre o envelhecimento normal e a fase mais inicial de demência, sendo uma fase importante para a precocidade diagnóstica. Nos últimos anos, pesquisas estão sendo desenvolvidas na busca de marcadores genéticos para esta zona de pré-demência, como os polimorfismos dos genes da apolipoproteína E (APOE) representada por 3 alelos (E2, E3, E4) e do colesterol 24S-hidroxilase (CYP46) com alelos T e C. Indivíduos portadores do APOE E4 tem fator de risco quatro vezes maior de desenvolver a Demência de Alzheimer e dez vezes mais probabilidade se tiver associado os polimorfismos dos genes APOE e CYP46. O objetivo deste estudo foi investigar a possível associação entre o polimorfismo dos genes CYP46(T/C), APOE E4 e a presença de DCL na população idosa do Distrito de Fernando de Noronha, totalizando uma seleção de 52 indivíduos. A avaliação clínica foi realizada através de exame físico, funcional e mental. Foram aplicados testes neuropsiquiátricos (Mini Exame do Estado Mental, Teste de Fluência Verbal, Teste do Relógio) e a identificação do genótipo dos polimorfismos do APOE e CYP46 pelo método de PCR-RFLP. Como resultados observou-se que 87% da amostra apresentou declínio cognitivo leve. No Mini Exame do Estado Mental...

ApoE, un modulador de la inflamación en la artritis inducida por colágeno

Genre, Fernanda
Fonte: Universidad de Cantabria Publicador: Universidad de Cantabria
Tipo: Tese de Doutorado
SPA
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La artritis reumatoide (AR) es una enfermedad autoinmune asociada con un alto índice de mortalidad pro eventos cardiovasculares. Los pacientes con AR suelen presentar dislipemia y disfunción endetelial. ApoE es una apolipoproteína involucrada en el metabolismo lipídico y que tiene además funciones inmunomoduladoras. Utilizando ratones deficientes en ApoE (dislipémicos) estudiamos su papel en un modelo experimental de AR inducida por colágeno (AIC). Los datos aportados en el presente trabajo apoyan la idea de que ApoE tiene la capacidad de modular negativamente la actividad inflamatoria de la AIC. Este efecto parece llevarse a cabo a través de la modulación, tanto de la inmunidad innata (como demuestra la disminución de la expresión de citocinas pro-inflamatorias), como de la inmunidad adaptativa (según indican los cambios en los perfiles de expresión en las articulaciones de citocinas características de las poblaciones Th1 y Th17 y en los isotipos de IgG en las respuestas humorales anti-CII)

Apoe isoforms in patients with psoriasis

Ferreira, J.C.P.; Torres, T.; Carvalho, C.A.; Bettencourt, A.; Leal, B.; Vasconcelos, C.; Costa, P.P.; Selores, M.; Silva, B.M.
Fonte: Wiley/ European Academy of Dermatology and Venereology Publicador: Wiley/ European Academy of Dermatology and Venereology
Tipo: Conferência ou Objeto de Conferência
Publicado em 03/07/2013 ENG
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Introduction: Psoriasis is a chronic inflammatory skin disease affecting 2–3% of the world population. Patients with psoriasis (Ps) have higher prevalence of lipid disorders when compared to unaffected individuals. These patients, especially those with severe and prolonged disease, have an increased morbidity and mortality from cardiovascular events. Apolipoprotein E (ApoE), a protein involved in lipid metabolism, cholesterol and phospholipid transport, has functionally relevant gene variants. It has been described that the e4 allele may increase the risk to develop atherosclerosis, and the e2 allele has been associated with hyperlipoproteinemia type III. An increased risk of psoriasis among persons with these two alleles has also been reported. Nevertheless, the role of ApoE in Psoriasis remains controversial. Objectives: The aim of this work was to investigate the relationship between APOE-e2/e3/e4 variants and psoriasis in a Portuguese population. Materials and Methods: A cohort of 178 unrelated (74 females, 104 males) severe psoriatic patients [according to the Psoriasis Area and Severity Index (PASI)] from Centro Hospitalar do Porto/Hospital de Santo Ant onio and 285 ethnically-matched healthy controls were studied. Genotyping of APOE was performed using a Polymerase chain reaction restriction fragment-length polymorphism (PCR-RFLP) assay. Results: The frequency of the e4 allele was significantly higher in patients than in controls [(11.5% vs. 7.6%)...

APOE genotypes and dyslipidemias in a sample of the Portuguese population

Rodrigues, M.O.; Fonseca, A.; Dias, Carlos Matias; Albergaria, I.; Martins, G.; Alpendre, M.L.; Martins, M. do C.
Fonte: Walter de Gruyter Publicador: Walter de Gruyter
Tipo: Artigo de Revista Científica
Publicado em /09/2005 ENG
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The objective of this work was to study the distribution of apolipoprotein E (APOE) genotypes in a sample of the Portuguese population, and its association with the dyslipidemias observed. Study participants were healthy users of local Public Health Laboratories in six regions of mainland Portugal (Porto, Vila Real, Viseu, Lisboa, Portalegre and Faro). A total of 779 men and 1153 women aged 15-74 years agreed to participate. Fasting lipid levels and APOE genotypes were determined centrally at the National Institute of Health in Lisboa. The frequency distribution of APOE alleles was: epsilon2=5.3%, epsilon3=84.9% and epsilon4=9.8%. Dyslipidemias were present in 66.6% of men and 60.7% of women. Comparison of APOE genotypes and relative allele frequencies showed that in dyslipidemic compared to normolipidemic subjects, the epsilon4 allele was more frequent in both sexes, although in a more pronounced way in men than in women due to higher frequencies of epsilon3/epsilon4 and epsilon4/epsilon4 genotypes. The known association of the epsilon4 allele with high cholesterol levels, the association of the epsilon2 allele with low cholesterol levels, and the association of the epsilon2 allele with high levels of triglycerides and low levels of high-density lipoprotein-cholesterol were confirmed in this study.

APOE genotype and entorhinal cortex volume in non-demented community-dwelling adults in midlife and early old age

Bunce, David; Anstey, Kaarin J.; Cherbuin, Nicolas; Gautam, Prapti; Sachdev, Perminder Singh; Easteal, Simon
Fonte: IOS Press Publicador: IOS Press
Tipo: Artigo de Revista Científica Formato: 8 pages
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The apolipoprotein E (APOE) ε4 allele is a risk factor for the neuropathological decline accompanying Alzheimer's disease (AD) while, conversely, the ε2 allele offers protection. One of the brain structures exhibiting the earliest changes associated with the disease is the entorhinal cortex. We therefore investigated the volumes of the entorhinal cortex and other structures in the medial temporal lobe including the parahippocampal gyrus, temporal pole, and inferior, middle, and superior temporal cortices, in relation to APOE genotype. Our main objectives were to determine if (a) volumes systematically varied according to allele in a stepwise fashion, ε2 > ε3 > ε4, and (b) associations varied according to age. We investigate this association in 627 non-demented community-dwelling adults in middle age (44 to 48 years; n = 314) and older age (64 to 68 years; n = 313) who underwent structural MRI scans. We found no evidence of APOE-related variation in brain volumes in the age groups examined. We conclude that if a ε2 > ε3 > ε4 pattern in brain volumes does emerge in non-demented adults living in the community in old age, it is not until after the age of 68 years.; NHMRC (National Health and Medical Research Council of Australia)

Polymorphism of the APOE locus in the Azores Islands (Portugal)

Bettencourt, Conceição; Montiel, Rafael; Santos, Cristina; Pavão, Maria Leonor; Viegas-Crespo, Ana Maria; Lopes, Paula Alexandra; Lima, Manuela
Fonte: American Association of Anthropological Genetics Publicador: American Association of Anthropological Genetics
Tipo: Artigo de Revista Científica
Publicado em /08/2006 ENG
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Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.; Our aim in this study is to report on the polymorphism of the APOE gene in the Azores Islands (Portugal) to obtain a population baseline of the existing variation in this locus, known to be one of the genetic determinants of plasma lipid levels. One hundred twenty-six Azorean individuals were typed for the APOE polymorphism using standard PCR-RFLP. Allele frequencies obtained for APOE*2, APOE*3, and APOE*4 were 6.75%, 83.73%, and 9.52%, respectively. The APOE*3/*3 genotype presented the highest frequency (69.84%), and the APOE*4/*4 genotype had the lowest frequency (0.79%). Genotype frequencies were in conformity with Hardy-Weinberg expectations. The observed genotype and allele frequencies were similar to those reported for other Iberian samples. Furthermore, Nei's gene diversity ((H) over cap = 0.2864 +/- 0.0351) was similar to that reported for samples from mainland Portugal. The data generated from this study will be of importance in the context of ongoing studies concerning the factors that influence lipid levels in the Azorean population.

APOE-ε4 polymorphism and cognitive deficit among the elderly population of Fernando de Noronha

Garcia,Anália Nusya; Silva,Helker Albuquerque da; Silva,Renan Carlos; Leal,Eliane Maria Medeiros; Rodrigues,Lorena; Silva,Vanessa Cavalcante da; Dellalibera,Edileine; Freitas,Elizabete Malaquias; Ataíde Jr,Luiz; Muniz,Maria Tereza Cartaxo
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2008 EN
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BACKGROUND: Polymorphism of the gene for apolipoprotein E (APOE) is an important risk factor for the development of Alzheimer's disease. The ε4 allele of the APOE gene has been linked with a number of neuropsychiatric illnesses, and also with stress and depression among geriatric populations. OBJECTIVE: To identify APOE-ε4 polymorphism and correlate this with cognitive deficit among the elderly population of the island of Fernando de Noronha. METHOD: Neuropsychiatric tests (mini-mental state examination, verbal fluency test and clock drawing test) were applied to 52 elderly people without Alzheimer's disease. DNA was isolated from peripheral blood and genotyping of APOE was done by the PCR-RFLP method. RESULTS: 87% of the elderly population (mean age 69.6±7.0) had cognitive deficit. CONCLUSION: The observed frequency of the ε4 allele was 10%, but the correlation between the presence of ε4 and cognitive deficit in this population was not statistically significant.

APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies

Jacquier,Martine; Arango,Diana; Villareal,Elsa; Torres,Orlando; Serrano,Martha Lucia; Cruts,Marc; Montañes,Patricia; Cano,Carlos; Rodriguez,Maria Nelcy; Serneels,Sally; Van Broeckhoven,Christine
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2001 EN
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OBJECTIVE: As the strength of the association between the APOE epsilon4 allele and Alzheimer's disease (AD) varies across ethnic groups, we studied if there was such an association in Colombian patients. METHOD: We performed apolipoprotein E (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53) diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44) had no significant cognitive impairment by medical interview and neuro-psychological testing. RESULTS: We found a high association (OR= 5.1 95%CI 1.9 -13.6) between APOE epsilon4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9%). A significant negative association was found between epsilon2 and AD (OR= 0.2 95% CI 0.05-0.75). CONCLUSION: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE epsilon4.

The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)

Risacher, Shannon L.; Kim, Sungeun; Shen, Li; Nho, Kwangsik; Foroud, Tatiana; Green, Robert C; Petersen, Ronald C.; Jack, Clifford R.; Aisen, Paul S.; Koeppe, Robert A.; Jagust, William J.; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Saykin
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
EN_US
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37.16%
Objective: Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort. Methods: Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints. Results: E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed. Conclusions: APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ...

Specific interaction of heterogeneous nuclear ribonucleoprotein A1 with the –219T allelic form modulates APOE promoter activity

Campillos, Mónica; Lamas, José Ramón; García, Miguel Ángel; Bullido, María Jesús; Valdivieso Amate, Fernando; Vázquez, Jesús
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artículo Formato: 122002 bytes; application/pdf
ENG
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The polymorphic –219T/G variant in the APOE promoter has been associated with variations in basal transcriptional activity as well as with the risk of developing Alzheimer’s disease, myocardial infarction and early-onset coronary heart disease. The molecular mechanisms underlying these effects are presently unknown. In this report, we show that nuclear extracts from Jurkat cells form a T-specific complex with a motif including the –219 site within the APOE promoter. By DNA-affinity chromatography and mass spectrometry, the human heterogeneous nuclear ribonucleoprotein hnRNPA1(A1) was identified as one component of the complex. In vitro binding analysis indicated that a fragment of A1 had a marked binding specificity for the T form. Interaction of A1 with this region is driven by an adjacent telomeric-like sequence; however, the presence of G, but not T, at –219 position inhibited this interaction. The differences in transcriptional activity between the –219T and –219G promoter allelic forms correlated with the expression levels of A1 in several cell lines; also, over-expression of A1 increased the activity of the T form relative to that of the G form. These results indicate that A1 transactivates APOE promoter activity by direct and specific interaction with the –219T site.; This work was supported by CICYT SAF 2000-0178 and 08.5/ 0065.1/2001 grants from Spanish Ministerio de Ciencia y TecnologõÂa and from Comunidad AutoÂnoma de Madrid...

Functional characterization of three single–nucleotide polymorphisms present in the human APOE promoter sequence: Differential effects in neuronal cells and on DNA– protein interactions.

Maloney, Bryan; Ge, Yuan-Wen; Petersen, Ronald D.; Hardy, John; Rogers, Jack T.; Pérez-Tur, Jordi; Lahiri, Debomoy K.
Fonte: Wiley-Blackwell Publicador: Wiley-Blackwell
Tipo: Artículo
ENG
Relevância na Pesquisa
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Variations in levels of apolipoprotein E (ApoE) have been tied to the risk and progression of Alzheimer’s disease (AD). Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene (APOE) promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter’s role in the human disease. We examine here three specific single–nucleotide polymorphisms within the human APOE promoter region, specifically at −219 (G/T), −427 (T/C), and at −491 (A/T) upstream from the +1 transcription start site. The −219 and −491 polymorphic variations have significant association with instance of AD, and −491AA has significant risk even when stratified for the APOEε4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The −491 and −219 polymorphisms may have an interactive effect in addition to any independent activity. DNA–protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the −491 and −219 polymorphic sites. This work’s significance lies in drawing connection among APOE promoter polymorphisms’ associations with AD to functional promoter activity differences and specific changes in DNA–protein interactions with cell culture-based assays. Taken together...