Polymorphisms of apolipoprotein E in the Afro-descendant population of Buenaventura, Colombia / Polimorfismos del gen de la apopoliproteína E en la población afrodescendiente de Buenaventura, Colombia

ABSTRACT Objetives: To estimate the frequency distribution, both allelic and genotypic, of the APOE gene in the Afro-descendant population of Buenaventura, Colombia. Methods: Three hundred and forty-eight Afro-descendant individuals were analyzed and the APOE locus was genotyped by PCR-RFLP. The allelic and genotypic frequencies were established by direct counting and the Hardy-Weinberg equilibrium was evaluated through X2 test. The frequencies obtained in this study were compared with frequencies reported for other Colombian populations through the Fisher's exact test. Results: The following allelic frequencies were observed: E3, 70.8%; E4, 21.4%, and E2, 7.8%. The genotypic frequencies were: E3/E3, 51.1%; E3/E4, 27.3%; E2/E3, 12.1%; E4/E4, 6%; E2/E4, 3.5%, and E2/E2, 0%. The entire examined population was found in Hardy-Weinberg equilibrium (P = .074), and significant differences were found in the allele E4 when comparing this population with the Amerindian and mestizo populations of Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla and Medellín (P< 0.0345). Conclusions: The allelic frequencies observed in this study were significantly different from the frequencies reported in other Colombian populations. The high representativeness of the E4 and E2 alleles validates the hypothesis that there are micro-evolutionary processes that have been acting on their frequencies and could be associated with susceptibility to neuropsychiatric diseases such as Alzheimer's disease, metabolic alterations of fats and/or coronary artery disease.

RESUMEN Objetivos: Estimar la distribución de frecuencias tanto alélicas como genotípicas del gen APOE en la población afrodescendiente de Buenaventura, Colombia. Métodos: Mediante la técnica de PCR-RFLP's se analizaron 348 individuos no relacionados de esta ciudad. Se realizó el cálculo de frecuencias alélicas y genotípicas y se evaluó el equilibrio de Hardy-Weinberg mediante la prueba de la X2. Se compararon las frecuencias alélicas obtenidas en el presente estudio con otras poblaciones de Colombia mediante el test exacto de Fisher. Resultados: Se reportaron las siguientes frecuencias alélicas: E2, 7,8%; E3, 70,8%, y E4, 21,4%. Las frecuencias genotípicas fueron: E3/E3, 51,1%; E3/E4,27,3%; E4/E4,6%; E2/E3,12,1%; E2/E4, 3,5%, y E2/E2, 0%. La población total se encontró en equilibrio de Hardy-Weinberg (p = 0,074), y se hallaron diferencias significativas en el alelo E4 al comparar esta población con las amerindias y mestizas de Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla y Medellín (p < 0,0345). Conclusiones: Las frecuencias alélicas observadas fueron significativamente diferentes de las frecuencias reportadas en otras poblaciones de Colombia. La alta representatividad de los alelos E4 y E2 validan la hipótesis de que hay procesos microevolutivos que han venido actuando en sus frecuencias y pueden estar asociadas con susceptibilidad a enfermedades neuropsiquiátricas como la enfermedad de Alzheimer, alteraciones metabólicas de las grasas y/o enfermedad coronaria.

Polimorfismos del gen de la apolipoproteína E en adultos mayores de 60 años con disminución de la memoria cognitiva y enfermedad de Alzheimer en diferentes poblaciones venezolanas / Apolipoprotein E polymorphisms in adults over 60 years of age with mild cognitive impairment and Alzheimer's disease in different Venezuelan populations

Introducción. La enfermedad de Alzheimer constituye un problema de salud pública que tiende a agravarse en el tiempo. Entre los factores genéticos de predisposición más importantes, se encuentra la presencia del alelo ε4 del gen APOE que codifica para la apoproteína E. Objetivo. Determinar las frecuencias alélicas y genotípicas de las isoformas de APOE en adultos mayores de 60 años con memoria cognitiva disminuida y Alzheimer, en la gran Caracas y en la comunidad indígena pemón de la zona Kamarata-Kanaimö, Estado Bolívar. Materiales y métodos. Se estudiaron 267 pacientes: 96 controles, 40 con memoria cognitiva disminuida y 108 con Alzheimer procedentes de Caracas, y 23 individuos de Kamarata-Kanaimö. Las isoformas de APOE se determinaron con el estuche AP1210Z: Seeplex ApoE genotyping™. Resultados. El alelo ε4 mostró asociación significativa con la memoria cognitiva disminuida (OR=5,03; IC95% 0,98-25,70) y la enfermedad de Alzheimer (OR=5,78; IC95% 1,24-26,85). Las frecuencias genotípicas de los grupos de control y con memoria cognitiva disminuida, fueron:ε3/ε3> ε3/ε4> ε2/ε4> ε3/ε2> ε4/ε4, y las del grupo con Alzheimer: ε3/ε3> ε3/ε4> ε4/ε4> ε2/ε4> ε3/ε2. En Kamarata-Kanaimö, el orden fue ε3/ε3> ε3/ε4> ε4/ε4 y no se encontró el alelo ε2. Conclusiones. Las frecuencias alélicas y genotípicas de APOE en la muestra tuvieron una distribución similar a la de otros estudios en Venezuela y las Américas. La ausencia del alelo ε2 en la comunidad indígena de Kamarata-Kanaimö amerita mayor investigación. Se constató la asociación positiva del alelo ε4 en personas con la enfermedad de Alzheimer y con memoria cognitiva disminuida. Conocer precozmente los pacientes portadores de este alelo puede ayudar a establecer medidas preventivas en nuestra población.

Introduction: Alzheimer's disease represents a serious public health problem that tends to worsen over time. Among the most important genetic predisposing factors is the presence of the ε4 allele of the apoprotein E gene (APOE). Objective: To determine the allelic and genotypic frequencies of the APOE isoforms in adults over 60 years old with mild cognitive impairment and Alzheimer's disease in Gran Caracas and in the indigenous Pemón community of the Kamarata-Kanaimö area, Bolívar State. Materials and methods: We studied 267 patients: 96 controls, 40 with mild cognitive impairment, 108 with Alzheimer's from Caracas, and 23 individuals from Kamarata-Kanaimö. The APOE isoforms were determined with the AP1210Z: Seeplex® ApoE Genotyping kit. Results: The allele ε4 showed a significant association with mild cognitive impairment (OR=5.03; 95% CI: 0.98-25.70) and EA (OR=5.78; 95% CI: 1.24-26.85). The genotype frequencies for the control and mild cognitive impairment groups were ε3/ε3> ε3/ε4> ε2/ε4> ε3/ε2> ε4/ε4, and for the Alzheimer's group, ε3/ε3> ε3/ε4> ε4/ε4> ε2/ε4> ε3/ε2 In Kamarata-Kanaimö, the order was ε3/ε3> ε3/ε4> ε4/ε4; the allele ε2 was not found in this group. Conclusions:APOE allelic and genotypic frequencies in our sample showed a similar distribution to those found in other studies in Venezuela and the Americas. The absence of the ε2 allele in the indigenous community of Kamarata-Kanaimö warrants further investigation. The positive association of the ε4 allele with both Alzheimer's and mild cognitive impairment was reinforced. The early determination of the ε4 allele carriers can help establish preventive measures in our population.

Relación de los niveles plasmáticos de homocisteína y apolipoproteína b-100 con el riesgo cardiovascular / Relationship of plasma levels of homocysteine and apolipoprotein b-100 with cardiovascular risk

INTRODUCCION: las enfermedades cardiovasculares son responsables del 31% de la mortalidad mundial, existen parámetros como la homocisteína y la Apolipoproteína B-100 que podrían tener utilidad en la predicción del riesgo. OBJETIVO: relacionar los niveles plasmáticos de Homocisteína y Apolipoproteína B-100 con el riesgo cardiovascular en pacientes que acuden a consulta externa del Hospital Univalle, durante julio-agosto del 2018 METODOLOGIA: el presente estudio es no experimental observacional, tipo prospectivo, transversal, con un enfoque de análisis positivista cuantitativo, con un universo de (N=133) que se redujo a una unidad de análisis de 81, que cumplieron con los criterios de inclusión y exclusión con un 6.83% de error máximo aceptable. RESULTADOS: el 52% de los pacientes fueron mujeres. La edad media de fue de 49,8 (Rango 25 a 83), el grupo etario predominante fueron los adultos mayores. Según el IMC los sujetos de estudio presentan sobre peso (n=31) y grado de obesidad 1 (n=24) más frecuentemente. Los niveles plasmáticos elevados de Apolipoproteína B en ambos sexos no muestran una diferencia significativa, mientras en que los de homocisteína la diferencia fue de 8:1. Se constato que los niveles séricos de la Apolipoproteína B-100 tienen una sensibilidad y especificidad bajas del 19.40% y 28.42%, mientas los de la homocisteína fueron del 14.29% y 27.27% respectivamente en comparación con la técnica convencional. CONCLUSIONES: los niveles plasmáticos de homocisteína y Apolipoproteína B-100 no son parámetros predictores de padecer riesgo cardiovascular

INTRODUCTION: cardiovascular diseases are responsible for 31% of world mortality, there are parameters such as homocysteine and Apolipoprotein B-100 that could be useful in predicting risk. OBJECTIVE: to relate the plasma levels of Homocysteine and Apolipoprotein B-100 with cardiovascular risk in patients who attend the outpatient clinic of the Univalle Hospital, during July-August 2018. METHODOLOGY: this study is non-experimental, observational, prospective, cross-sectional, with a quantitative positivist analysis approach, with a universe of (N=133) that was reduced to an analysis unit of 81, who met the inclusion criteria. and exclusion with a 6.83% maximum acceptable error. RESULTS: 52% of the patients were women. The mean age was 49.8 (range 25 to 83), the predominant age group was the elderly. According to the BMI, the study subjects are overweight (n=31) and obesity grade 1 (n=24) more frequently. The elevated plasmatic levels of Apolipoprotein B in both sexes do not show a significant difference, while in those of homocysteine the difference was 8:1. It was found that the serum levels of Apolipoprotein B-100 have a low sensitivity and specificity of 19.40% and 28.42%, while those of homocysteine were 14.29% and 27.27% respectively compared to the conventional technique. CONCLUSIONS: plasma levels of homocysteine and Apolipoprotein B-100 are not predictors of cardiovascular risk.

Doença de Alzheimer de início precoce (DAIP): características neuropatológicas e variantes genéticas associadas / Early-onset Alzheimer's Disease (EOAD): neuropathological characteristics and associated genetic variants

RESUMO A doença neurodegenerativa mais comum no mundo é a doença de Alzheimer (DA), e 10% dos casos apresentam sintomas antes dos 65 anos, quase todos com associação genética, com hereditariedade autossômica dominante e penetrância entre 92 a 100% dos portadores. Na presente revisão, realizamos uma busca sobre as variantes genéticas associadas à doença de Alzheimer de início precoce (DAIP), enfatizando as características associadas mais importantes e as principais mutações já descritas. Os genes mais comumente relacionados com o surgimento da DAIP são APP, PSEN1, PSEN2 e MAPT, e mutações nestes afetam o metabolismo e a estrutura destas proteínas, resultando em acúmulos de peptídeo Aβ que causam inflamação e toxicidade no cérebro, levando à ativação da micróglia e promovendo a liberação de fatores neurotóxicos e pró-inflamatórios que aceleram a neurodegeneração. O gene PSEN1 é responsável por 70% das mutações conhecidas da DAIP, sendo a L166P associada à idade de ocorrência da doença abaixo dos 30 anos. Mutações em APP levam à agregação da proteína em placas neurodegenerativas. Todas as mutações descritas para MAPT estão associadas a um aumento dos emaranhados neurofibrilares. O polimorfismo E4 da Apolipoproteína E (APOE) influencia o aumento no risco de DAIP elevando as chances em três vezes para portadores heterozigotos e entre oito a dez vezes para os homozigotos. Apenas 5% das mutações associadas à DAIP são conhecidas, e novos estudos apresentam outros genes candidatos, bem como a importância de alterações epigenéticas na gênese desta doença.

SUMMARY The most common neurodegenerative disease in the world is Alzheimer's Disease (AD). Ten percent of Alzheimer patients experience symptoms before the age of 65, and almost all of them present genetic features of autosomal dominant inheritance nature, and penetrance of 92 to 100%. In the present review, we searched for genetic variants associated with early onset Alzheimer's disease (EOAD), emphasizing the most important characteristics and the main mutations. The genes most commonly related to the onset of EOAD are APP, PSEN1, PSEN2 and MAPT, whose mutations affect the metabolism and structure of these proteins. This process results in accumulations of Aβ peptide that leads to activation of the microglia and release of neurotoxic and pro-inflammatory factors that accelerate neurodegeneration. The PSEN1 gene is responsible for 70% of the known mutations in EOAD, while L166P is associated with below 30 years as the starting age of occurrence. APP mutations lead to protein aggregation in neurodegenerative plaques. All of the mutations described for MAPT are associated with an increase in neurofibrillary tangles. The E4 polymorphism of Apolipoprotein E (APOE) influences an increased risk of EOAD increasing up to three times the chances for heterozygous, and between eight and ten times for homozygotes carriers. Only 5% of the mutations associated with EOAD are known; new studies will show other candidate genes, as well as the importance of epigenetic factors changes in the etio-pathogenesis of this disease.

Apolipoproteína B: sus ventajas en el manejo del riesgo cardiovascular aterosclerótico / Apolipoprotein B: its advantages in the assessment of atherosclerotic cardiovascular risk / Apolipoproteína B: suas vantagens no manejo do risco cardiovascular aterosclerótico

Resumen Se analiza la determinación de apolipoproteína B (Apo B) en la evaluación y tratamiento de la enfermedad cardiovascular aterosclerótica (ECVA) con respecto a tres aspectos: a) marcador de riesgo aterogénico; b) ventajas sobre los lípidos; c) utilidad en el laboratorio bioquímico. Apo B participa en la aterogénesis. Habitualmente las partículas lipoproteicas aterogénicas se evalúan por su contenido en colesterol pero su masa por partícula es muy variable. Sin embargo, cada partícula tiene una molécula de Apo B por lo que es un estimador de su número y marcador de riesgo. Apo B desempeña un rol causal y explica mejor que el colesterol LDL (C-LDL) la relación etiológica con la enfermedad, tiene mayor capacidad discriminante que los lípidos, agregación familiar y mejor parámetro para el manejo del tratamiento en presencia de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólico, obesidad y diabetes. Puede determinarse sin ayuno previo con trazabilidad respecto de un patrón de referencia, comparabilidad y armonía de los resultados entre los laboratorios y menor error analítico que el colesterol no-HDL. C-LDL sigue siendo el objetivo primario para la evaluación y tratamiento del riesgo aterogénico. Por consenso se han informado los valores de corte para Apo B según categorías de riesgo de ECVA y se recomendó su uso cuando sea posible determinarla. Apo B es un excelente marcador de riesgo aterogénico, presenta mayor exactitud y precisión que los lípidos y su inclusión en el manejo de casos clínicos específicos contribuye a mejorar la calidad del tratamiento.

Abstract The determination of apolipoprotein B (Apo B) in the evaluation and treatment of atherosclerotic cardiovascular disease (ACVD) is analyzed, referring to three aspects: a) marker of atherogenic risk; b) advantages over lipids; c) utility in the biochemical laboratory. Apo B participates in atherogenesis. Atherogenic lipoprotein particles are usually evaluated for their cholesterol content, but their mass per particle is highly variable. However, each particle has an Apo B molecule so it is an estimator of its number and a marker of risk. Apo B plays a causal role and explains better than LDL cholesterol (LDL-C) the etiological relationship with the disease; it has a greater discriminating capacity than lipids, family aggregation and it is a better parameter for the management of treatment in the presence of LDL-C<70 mg/dL, moderate hypertriglyceridemia, metabolic syndrome, obesity, and diabetes. It can be determined without prior fasting with traceability to a reference standard, comparability and harmony of results between laboratories and lower analytical error than non-HDL cholesterol. LDL-C remains the primary endpoint for the evaluation and treatment of atherogenic risk. By consensus, cut-off values for Apo B have been reported according to ACVD risk categories and its use was recommended when it is possible to determine it. Apo B is an excellent marker of atherogenic risk, it has greater accuracy and precision than lipids and its inclusion in the management of specific clinical cases contributes to improving the quality of treatment.

Resumo A determinação da apolipoproteína B (Apo B) na avaliação e tratamento da doença cardiovascular aterosclerótica (DCVA) é analisada, referindo-se a três aspectos: a) marcador de risco aterogênico; b) vantagens sobre os lipídios; c) utilidade no laboratório bioquímico. Apo B participa da aterogênese. As partículas de lipoproteína aterogênica são geralmente avaliadas quanto ao seu conteúdo de colesterol, mas sua massa por partícula é altamente variável. No entanto, cada partícula possui uma molécula de Apo B, por isso é um estimador de seu número e um marcador de risco. A Apo B tem papel causal e explica melhor que o colesterol LDL (C-LDL) a relação etiológica com a doença, tem maior capacidade discriminante que os lipídios, agregação familiar e melhor parâmetro para o manejo do tratamento na presença de C-LDL<70 mg/dL, hipertrigliceridemia moderada, síndrome metabólica, obesidade e diabetes. Pode ser determinado sem jejum prévio com rastreabilidade a respeito de um padrão de referência, comparabilidade e harmonia de resultados entre laboratórios e menor erro analítico do que o colesterol não-HDL. O C-LDL continua sendo o objetivo primário para a avaliação e tratamento do risco aterogênico. Por consenso, os valores de corte da Apo B foram reportados de acordo com as categorias de risco de DCVA e seu uso foi recomendado quando possível. A Apo B é um excelente marcador de risco aterogênico, possui maior acurácia e precisão que os lipídeos e sua inclusão no manejo de casos clínicos específicos contribui para a melhoria da qualidade do tratamento.

Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review / Patogênese, achados histopatológicos e modalidades de tratamento da glomerulopatia por lipoproteínas: Uma revisão

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.

Distribution of polymorphism rs693 of ApoB gene in a sample of Colombian Caribbeans / Distribución del polimorfismo rs693 en el gen de la apolipoproteína B en una muestra caribeños colombianos

Abstract Introduction: Several studies have reported that the single nucleotide polymorphism rs693 of Apo lipoprotein B gene is associated with high levels of plasma lipids and high body mass index, which are risk factors for cardiovascular diseases. The distribution of this single nucleotide polymorphism and its association with the phenotype depend on the genetic background of each population. Objective: To evaluate the distribution of single nucleotide polymorphism rs693 and its association with lipid profile and body mass index in a sample of Colombian Caribbeans. Methods: 108 non-related adult subjects of both gender were included in this study. Body mass index and lipid profile that included total cholesterol, triglycerides, Low Density Lipoprotein and High Density Lipoprotein were determined. The single nucleotide polymorphism rs693 was determined by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism from genomic DNA followed by digestion with the restriction enzyme XbaI. The chi-square test was used to analyze the genotype distribution of rs693 and the genotype-phenotype association was evaluated through different inheritance model. Results: The genotype frequencies for single nucleotide polymorphism rs693 were CC (45.0%), TT (16.5%) and CT (38.5%). The allele frequencies were C (64.0%) and T (36.0%). The single nucleotide polymorphism was in Hardy-Weinberg equilibrium in the studied sample. No association of the single nucleotide polymorphism rs693 with lipid profile nor the body mass index was found (p >0.05). Conclusion: There is no significant association between single nucleotide polymorphism rs693 and body mass index nor lipid profile, in a sample of Colombian Caribbeans.

Resumen Introducción: Varios estudios han informado que el polimorfismo de un solo nucleótido rs693 del gen de la apolipoproteína B se asocia con altos niveles de lípidos plasmáticos e índice de masa corporal, los cuales son factores de riesgo para enfermedades cardiovasculares. La distribución de este polimorfismo y su asociación con el fenotipo dependen del antecedente genético de cada población. La población caribeña colombiana es producto de la mezcla de tres grupos étnicos principales: africano, amerindio y caucásico. Objetivo: Evaluar la distribución del polimorfismo rs693 y su asociación con el perfil lipídico y el índice de masa corporal en una muestra de sujetos caribeños colombianos. Métodos: Fueron incluidos en este estudio 108 sujetos adultos de ambos sexos y no relacionados. Se determinaron el índice de masa corporal y el perfil lipídico; de éste se incluyó colesterol total, triglicéridos, lipoproteínas de baja densidad y lipoproteína de alta densidad. El polimorfismo rs693 se determinó mediante Reacción en Cadena de la Polimerasa del ADN genómico seguida por digestión con la enzima de restricción XbaI. Se utilizó la prueba de ji cuadrado para analizar la distribución del genotipo de rs693 y se evaluó la asociación genotipo-fenotipo a través de diferentes modelos de herencia. Resultados: Las frecuencias genotípicas para rs693 fueron CC (45.0%), TT (16.5%) y TC (38.5%). Las frecuencias alélicas fueron C (64.0%) y T (36.0%). El polimorfismo rs693 estaba en equilibrio de Hardy-Weinberg en la muestra estudiada y no presentó asociación con el perfil lipídico ni con el índice de masa corporal (p >0.05). Conclusión: No existe asociación significativa del polimorfismo rs693 con el índice de masa corporal ni con el perfil lipídico en una muestra de caribeños colombianos.

APOL1 risk variants and kidney disease: what we know so far / Variantes de risco APOL1 e doença renal: o que sabemos até agora

ABSTRACT There are striking differences in chronic kidney disease between Caucasians and African descendants. It was widely accepted that this occurred due to socioeconomic factors, but recent studies show that apolipoprotein L-1 (APOL1) gene variants are strongly associated with focal segmental glomerulosclerosis, HIV-associated nephropathy, hypertensive nephrosclerosis, and lupus nephritis in the African American population. These variants made their way to South America trough intercontinental slave traffic and conferred an evolutionary advantage to the carries by protecting against forms of trypanosomiasis, but at the expense of an increased risk of kidney disease. The effect of the variants does not seem to be related to their serum concentration, but rather to local action on the podocytes. Risk variants are also important in renal transplantation, since grafts from donors with risk variants present worse survival.

RESUMO Existem importantes diferenças na doença renal crônica entre caucasianos e afrodescendentes. Foi amplamente aceito que isso ocorreu devido a fatores socioeconômicos, mas estudos recentes mostraram que as variantes gênicas da apolipoproteína L-1 (APOL1) estão fortemente associadas à glomeruloesclerose segmentar e focal, nefropatia associada ao HIV, nefroesclerose hipertensiva e nefrite lúpica na população afrodescendente. Essas variantes chegaram à América do Sul através do tráfico intercontinental de escravos, e proporcionaram uma vantagem evolutiva aos portadores, protegendo contra formas de tripanossomíase, mas à custa de um maior risco de doença renal. O efeito das variantes não parece estar relacionado à sua concentração sérica, mas sim à sua ação local sobre os podócitos. Variantes de risco também são importantes no transplante renal, já que enxertos de doadores com variantes de risco apresentam pior sobrevida.

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.

Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.

Marcadores de fase aguda en niños y adolescentes obesos con trastornos metabólicos / Acute phase markers in obese children and adolescents with metabolic disorders

Introducción. La obesidad es un problema de salud pública mundial y la enfermedad crónica no transmisible más frecuente. Se asocia con la elevación de proteínas inflamatorias de fase aguda y citocinas proinflamatorias. Objetivo. Evaluar los niveles de proteínas de fase aguda en niños y adolescentes obesos con esteatosis hepática y síndrome agudo metabólico. Metodología. Se incluyeron 45 niños con índice de masa corporal ≥ percentil 95, de edades entre 5,0 y 15,5 años. Se determinaron reactantes de fase aguda: proteína C reactiva, haptoglobina, a-2 macroglobulina y apolipoproteína A-1, y se realizó una ecografía para evaluar la esteatosis hepática. Resultados. Todos los pacientes mostraron una elevación de proteína C reactiva. Los pacientes con síndrome metabólico también tuvieron un incremento en la apolipoproteína A-1 y la haptoglobina. Los pacientes con esteatosis hepática tuvieron un aumento significativo en la a-2 macroglobulina además de la protenína C reactiva.

Introduction. Obesity is a worldwide public health problem and the most common non-communicable chronic disease. It is associated with an increase in inflammatory acute phase proteins and proinflammatory cytokines. Objective. To assess the levels of acute phase proteins in obese children and adolescents with hepatic steatosis and metabolic syndrome. Methodology. Forty-five children with a body mass index ≥ 95th percentile aged 5.0-15.5 years were included. The following acute phase reactants were determined: C-reactive protein, haptoglobin, alpha-2-macroglobulin, and apolipoprotein A-1; besides, an ultrasound was done to assess hepatic steatosis. Results. C-reactive protein levels increased in all patients. Patients with metabolic syndrome also had high levels of apolipoprotein A-1 and haptoglobin. Patients with hepatic steatosis had a significant increase in alpha-2-macroglobulin in addition to high C-reactive protein.

Rol del enterocito en la dislipidemia de la diabetes mellitus tipo 2 / Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia

En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Biomarcadores y marcadores de imagen de la enfermedad de Alzheimer / Biomarkers and image markers of Alzheimer's disease

Este artículo presenta un análisis desde el punto de vista bibliográfico de marcadores y biomarcadores de la enfermedad de Alzheimer (EA). Las metodologías usadas fueron los marcadores de imágenes (Resonancia Magnética y Tomografía por emisión de positrones) y biomarcadores de la proteína BA42, de la proteína Tau y de la Apoliproteína E (ALPE). De esta manera, son de importancia los niveles de BA42 disminuidos, la Tau incrementada, los polimorfismos de ALPE y las alteraciones constatadas en los marcadores de imagen, como factores de riesgo esenciales para el desarrollo de la EA. Se realiza una revisión de la literatura con respecto a los hallazgos clínicos de esta enfermedad.

This article presents a bibliographical analysis of markers and biomarkers of Alzheimer's disease (AD). The methodologies used were the imaging markers (Magnetic Resonance and Positron Emission Tomography) and biomarkers of the BA42 protein, Tau protein and Apoliprotein E (ALPE). Thus, decreased levels of BA42, increased Tau, ALPE polymorphisms, and alterations in imaging markers are important as risk factors for the development of AD. A review of the literature is made regarding the clinical findings of this disease.

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia / O efeito do extrato de semente de uva vermelha na atividade do soro paraoxonase em doentes com hiperlipidemia leve a moderada

ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

RESUMO: CONTEXTO E OBJETIVO: Extrato de semente de uva vermelha (RGSE) contém complexos de proantocianidinas oligoméricas como classe de flavonoides. Estes compostos são antioxidantes potentes e exercem muitos efeitos de promoção da saúde. Este estudo visou determinar os efeitos de RGSE nos níveis séricos de triglicérides (TG), colesterol total (TC), colesterol de lipoproteína alta-densidade (HDL-C), colesterol de lipoproteína baixa-densidade (LDL-C), apolipoproteína AI (apo-AI) e atividade de paraoxonase (PON) em pacientes com hiperlipidemia leve a moderada (MMH). DESENHO E LOCAL: Estudo clínico randomizado duplo-cego controlado com placebo, realizado no Hospital Shahid-Modarres (Teerã, Irã) e na Universidade de Ciências Médicas de Tabriz. Setenta pacientes com MMH foram aleatoriamente designados para receber tratamento (200 mg/dia de RGSE) ou placebo durante oito semanas. RESULTADOS: Elevação significativa nos níveis séricos de apo-AI (P = 0,001), HDL-C (P = 0,001) e atividade de PON (P = 0,001) e diminuição marcada nas concentrações de TC (P = 0,015), TG (P = 0,011) e LDL-C (P = 0,014) foram encontradas nos casos. Atividade de PON mostrou correlação significativa com apo-AI (r = 0,270; P < 0,01) e HDL-C (r = 0,45; P < 0,001). Diferenças significativas entre os grupos RGSE e controle (antes e após tratamento) para TC (P = 0,001), TG (P = 0,001), PON (P = 0,03), apo-AI (P = 0,001) e LDL-C (P = 0,002) foram observadas. CONCLUSÃO: É possível que RGSE aumente atividade de PON principalmente através da elevação dos níveis de HDL-C e apo-AI em pacientes MMH. Ele pode, assim, ter efeitos benéficos potenciais na prevenção de estresse oxidativo e aterosclerose nesses pacientes.

Apolipoprotein E polymorphism and functional disability in Brazilian elders: the Bambuí Health and Aging Study / Polimorfismo da apolipoproteína E e incapacidade funcional em idosos brasileiros: Projeto Bambuí / Polimorfismo de la apolipoproteína E e incapacidad funcional en los ancianos brasileños: Proyecto Bambuí

Abstract Numerous studies have associated the apolipoprotein E (apoE) ε4 allele with worse health status, but few have assessed the existence of genotype-dependent variations in functional performance. Among participants in the Bambuí Health and Aging Study, Minas Gerais State, Brazil, 1,408 elderly underwent apoE genotyping. Functionality was assessed with a questionnaire, and individuals were classified as dependent in basic activities of daily living (BADLs), instrumental activities of daily living (IADLs), and mobility. The association between apoE genotype and functional status was assessed by logistic regression, taking confounding factors into account. Presence of ε4 allele was associated with lower odds of mobility deficit (OR = 0.65; 95%CI: 0.47-0.92) in the adjusted analysis. There were no significant differences in relation to presence of dependency in BADLs and IADLs. The reasons are not entirely understood, but they may involve the role of ε4 allele as a "thrifty gene" in a sample exposed to high risk of infectious and nutritional diseases in the past.

Resumo Inúmeros estudos têm associado o alelo ε4 da apolipoproteína E (apoE) com pior condição de saúde, mas poucos avaliaram a existência de variações genótipo-dependentes no desempenho funcional. Entre os participantes da coorte de Bambuí, Minas Gerais, Brasil, 1.408 idosos foram submetidos à genotipagem da apoE. A funcionalidade foi avaliada por questionário, sendo os indivíduos classificados em dependentes para atividades básicas da vida diária (ABVDs), atividades instrumentais da vida diária (AIVDs) e mobilidade. A associação entre o genótipo da apoE e o estado funcional foi avaliada pela regressão logística, considerando variáveis de confusão. A presença do alelo ε4 foi associada a uma menor chance de déficit na mobilidade (OR = 0,65; IC95%: 0,47-0,92), na análise ajustada. Não houve diferenças significativas em relação à presença de incapacidades em ABVDs e AIVDs. Os motivos não estão completamente compreendidos, mas podem envolver o seu papel como um "thrifty gene" em uma amostra exposta a um risco elevado de doenças infecciosas e nutricionais no passado.

Resumen Innumerables estudios han asociado el alelo ε4 de la apolipoproteína E (apoE) con una peor condición de salud, pero pocos evaluaron la existencia de variaciones genotipo-dependientes en el desempeño funcional. Entre los participantes de la cohorte de Bambuí, Minas Gerais, Brasil, 1.408 ancianos fueron sometidos a una determinación del genotipo de la apoE. La funcionalidad fue evaluada por cuestionario, siendo los individuos clasificados en: dependientes para actividades básicas de la vida diaria (ABVDs), actividades instrumentales de la vida diaria (AIVDs) y movilidad. La asociación entre el genotipo de la apoE y el estado funcional fue evaluada por regresión logística, considerando variables de confusión. La presencia del alelo ε4 fue asociada a una menor probabilidad de déficit en la movilidad (OR = 0,65; IC95%: 0,47-0,92) en el análisis ajustado. No hubo diferencias significativas en relación con la presencia de incapacidades en ABVDs y AIVDs. Los motivos no están completamente claros, pero pueden están involucrados por su papel como un "thrifty gene" en una muestra expuesta a un riesgo elevado de enfermedades infecciosas y nutricionales en el pasado.

Hipobetalipoproteinemia primária: relato de caso / Primary Hypobetalipoproteinemia: a case report

Descrevemos o caso de uma paciente de 19 anos diagnosticada com hipobetalipoproteinemia primária. A paciente apresentava sintomas compatíveis com a doença como diarreia desde o primeiro mês de vida, défice de crescimento e retinopatia. A biópsia duodenal evidenciou presença de vacúolos lipídicos intraepiteliais, os quais foram altamente sugestivos para o diagnóstico. Os exames complementares evidenciaram disfunção hepática, baixos níveis séricos de triglicerídeos, e de colesterol total e frações. Após a dosagem de apolipoproteína B abaixo dos valores da normalidade, aliada a clínica e exames complementares, o diagnóstico foi realizado. A relativa escassez de dados na literatura em nosso meio, atrelada à raridade da doença, ilustra a relevância deste relato de caso, somado à importância do diagnóstico precoce

The case of a 19-year-old female patient who was diagnosed with Primary Hypobetalipoproteinemia (HBL) is described.The patient presented symptoms that were consistent with the disease, such as diarrhea from the very first month of life, growth failure and retinopathy. The duodenal biopsy showed the presence of intraepithelial lipid vacuoles that were highly suggestive of the diagnosis. Further tests showed liver dysfunction, low serum levels of triglycerides and total cholesterol and fractions. After the dosage of Apolipoprotein B below normal values, and clinical exam along with laboratory tests, the diagnosis was made. The lack of data in the literature and the rarity of the disease illustrate the importance of this case report,and of an early diagnosis.

Association between LDL-C, Non HDL-C, and Apolipoprotein B Levels with Coronary Plaque Regression / Associação entre Níveis De LDL-C, Não-HDL-C E Apolipoproteína B com Regressão de Placa Coronariana

Previous reports have inferred a linear relationship between LDL-C and changes in coronary plaque volume (CPV) measured by intravascular ultrasound. However, these publications included a small number of studies and did not explore other lipid markers.

Estudos prévios sugerem uma relação linear entre o LDL-C e mudanças no volume de placa coronariana (VPC) medido por ultrassonografia intravascular. No entanto, estas publicações incluíram um número pequeno de estudos e não exploraram outros marcadores lipídicos.

Apolipoprotein A-I mimetic peptide D4F protects macrophages from oxi-dized low-density lipoprotein-induced apoptosis by inhibiting caspase-12 / 中国病理生理杂志

[ABSTRACT]AIM:ToinvestigatetheeffectofD4F,anapolipoproteinA-Imimeticpeptide,onoxidizedlow-density lipoprotein ( ox-LDL)-induced macrophage apoptosis and activation of caspase-12, a key molecule in endoplasmic reticulum stress ( ERS )-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms. METHODS:RAW264.7 macrophages were pretreated with D4F (12.5, 25 and 50 mg/L), 4-phenylbutyric acid (PBA, 5 mmol/L) or diphenyleneiodonium ( DPI, 5 μmol/L) for 1 h and then treated with ox-LDL (100 mg/L) or tunicamycin ( TM, 4 mg/L) for 24 h.The cell viability and apoptosis were determined by MTT assay and TUNEL detection, respective-ly.The levels of malondialdehyde ( MDA) and reactive oxygen species ( ROS) in the cells and the activities of superoxide dismutase ( SOD) and nicotinamide adenine dinucleotide phosphate ( NADPH) oxidase were determined.The protein level of caspase-12 was examined by Western blot analysis.RESULTS: Similar to the ERS inhibitor PBA, D4F protected RAW264.7 macrophages from ox-LDL or TM ( an ERS inducer)-induced decrease in the viability and increase in apoptotic rate in a dose-dependent manner.Like DPI (an oxidative stress inhibitor), D4F significantly inhibited ox-LDL-induced ox-idative stress, as expressed by the decreased generation of ROS and MDA ( P<0.01) , the increased activity of SOD and the decreased activity of NADPH oxidase (P<0.05).Moreover, similar to PBA and DPI, D4F significantly suppressed ox-LDL-induced activation of caspase-12 in a concentration-dependent manner ( P<0.05) .Furthermore, D4F also inhibi-ted the caspase-12 activation induced by TM (P<0.05).CONCLUSION: D4F inhibits macrophage apoptosis induced by ox-LDL, and the mechanism is at least partially by reducing oxidative stress and inhibiting the activation of caspase-12.

Aerobic fitness modulates the association between APOE genotypes and serum lipemia in adolescents / Aptidão física aeróbica modula a associação entre genótipos da APOE e lipemia sérica em adolescentes / La condición física aeróbica modula la asociación entre los genotipos APOE y lipemia sérico en adolescentes

The purpose of this study was to analyze the association between APOE alleles and serum lipemia in adolescents with low and adequate aerobic fitness. The sample was comprised of 105 boys and 151 girls (49% and 46% from rural area) of European ancestry, aged 11 to 17 years, and classified according to: 1) APOE genotype: group ε2 (ε2/3+ε2/2), ε3 (ε3/3), and ε4 (ε3/4+ε4/4); 2) aerobic fitness: adequate or low; 3) serum lipemia: elevated total cholesterol (TC), low-density lipoprotein (LDL) and triglycerides, and low high-density lipoprotein (HDL). The results showed that aerobic fitness modulates the association between APOE alleles and serum lipemia in adolescents, suggesting that adequate aerobic fitness levels exert a greater effect of reducing TC and LDL in ε2 carriers, as well as of increasing HDL and reducing triglycerides in ε3 and ε4 carriers...

"Aptidão física aeróbica modula a associação entre genótipos da APOE e lipemia sérica em adolescentes." O objetivo deste estudo foi analisar a associação entre os alelos da APOE e a lipemia sérica em adolescentes com baixa e adequada aptidão aeróbia. Amostra: 105 rapazes(49% da área rural) e 151 moças (46% da área rural) descendentes de europeus, com idade de 11 a 17 anos, classificados de acordo com 1) genótipo da APOE: grupo ε2 (ε2/3+ε2/2), ε3 (ε3/3), e ε4 (ε3/4+ε4/4); 2) aptidão aeróbia: adequada ou baixa; 3) lipemia sérica: elevados colesterol total (CT), lipoproteína de baixa densidade (LDL) e triglicérides, e baixa lipoproteína de alta densidade (HDL). Os resultados demonstram que a aptidão aeróbia modula a associação dos alelos da APOE com a lipemia sérica de adolescentes, sugerindo que níveis adequados de aptidão aeróbia têm efeito maior em reduzir CT e LDL elevados nos portadores do alelo ε2, bem como o efeito maior em aumentar HDL e reduzir triglicerídeos naqueles com ε3 e ε4...

"La condición física aeróbica modula la asociación entre los genotipos APOE y lipemia sérico en adolescentes." El objetivo fue analizar la asociación entre los alelos APOE y la lipemia sérica en adolescentes con baja y adecuada condición aeróbica. La muestra fue composta de 105 niños (49% de las zonas rurales) y 151 niñas (46% de las zonas rurales) de origen europeo, con edades entre 11-17 años, clasificados de acuerdo con 1) el genotipo APOE: grupo ε2 (ε2 / 3 + ε2 / 2), ε3 (ε3 / 3), y ε4 (ε3 / ε4 + 4/4); 2) la condición aeróbica: adecuada o baja; 3) suero lipémico: colesterol (CT), lipoproteínas de baja densidad (LDL) y los triglicéridos elevados y lipoproteínas de alta densidad (HDL) bajo. Los resultados muestran que la capacidad aeróbica modula la asociación de los alelos APOE con la lipemia de los adolescentes, lo que sugiere que niveles adecuados de capacidad aeróbica tienen mayor efecto en la reducción de CT y LDL elevados en el alelo ε2, y el mayor efecto para aumentar el HDL y la reducción de los triglicéridos en aquellos con ε3 y ε4...

Prevalencia de variantes en el gen de la apolipoproteína E (APOE) en adultos de la población general del área urbana de Medellín (Antioquia) / Prevalence of Variants in the Apolipoprotein E (APOE) Gene in a General Population of Adults from an Urban Area of Medellin (Antioquia)

Objetivos: Determinar las frecuencias alélicas y genotípicas del gen de la apolipoproteína E (APOE) en adultos de Medellín durante el año 2010. Métodos: Se tomó una muestra representativa de la población adulta de Medellín, mediante un muestreo polietápico estratificado por conglomerados. Se realizó genotipificación para APOE a cada uno de los sujetos participantes. En el análisis de frecuencias y asociación, se tuvo en cuenta el diseño muestral. Resultados: Las frecuencias de los alelos E2, E3 y E4 de APOE fueron del 3,9, el 92,0 y el 4,1% respectivamente. Las frecuencias genotípicas fueron: 2/2, el 0,2%; 2/3, el 6,8%; 2/4, el 0,6%; 3/3, el 85,0%; 3/4, el 7,2%, y 4/4, el 0,3%. Conclusiones: Las frecuencias alélicas y genotípicas de APOE en adultos de Medellín tienen una distribución similar a las reportadas en poblaciones suramericanas, y son datos que tienen valor para conocer el impacto poblacional de estas variantes genéticas en distintos trastornos psiquiátricos.

Objective: To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. Methods: A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. Results: The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. Conclusions: The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.

Las bebidas cola aceleran el crecimiento de la placa aterosclerótica en ratones ApoE-/- / Cola Beverages Accelerate Growth of the Atherosclerotic Plaque in ApoE-/- Mice

Introducción Los hábitos de alimentación poco saludables durante la infancia y la juventud se han suge­rido como favorecedores de las complicaciones ateroscleróticas en edades más avanzadas. El creciente consumo de bebidas cola en las últimas décadas se ha asociado con el desarrollo de obesidad e incremento en la incidencia de aterosclerosis y enfermedades cardiovasculares. A su vez, se sabe que existe correspondencia entre el consumo de estas bebidas y etapas de la vida, el cual es mayor en los niños, los adolescentes y los adultos jóvenes. Objetivo Evaluar el efecto del consumo de bebidas cola sobre la aterosclerosis. Material y métodos Se distribuyeron ratones ApoE-/- (8 semanas de edad) en tres grupos según el consumo libre de agua (A), bebida cola azucarada (C) y bebida cola edulcorada light (L). Al cabo de 8 semanas las bebidas cola se reemplazaron por agua. Los ratones fueron sacrificados secuencialmente: antes del tratamiento (8 semanas de edad) y luego de su interrupción (16, 20, 24 y 30 semanas de edad). Se extrajeron la aorta ascendente y el hígado. Se calculó la relación entre el área de la placa aórtica y el espesor de la capa media (relación placa/media). Se evaluó la inflamación del parénquima hepático según la escala de NASH. Resultados La relación placa/media varió según la bebida (F2,54 = 3,433, p < 0,04) y la edad (F4,54 = 5,009, p < 0,03) y fue mayor en los grupos C y L (p < 0,05 a las 16 y 20 semanas, p < 0,01 a las 24 y 30 semanas). La inflamación del parénquima hepático (F2,9 = 13,29, p < 0,002) y portal (F2,9 = 6,30, p < 0,02) aumentó cinco y dos veces, respectivamente, en función del tiempo (p < 0,01 y p < 0,03) entre las semanas 20 y 30, en contraste con la esteatosis y el daño hepatocelular, que no se modificaron. El grupo A (evolución natural de la aterosclerosis) se caracterizó por la aceleración del crecimiento del área de placa en paralelo con un rápido aumento de la inflamación hepática alrededor de la semana 20. Conclusiones El consumo de bebidas cola en ratones ApoE-/- entre las semanas 8 y 16 de edad aumentó la tasa de progresión de la aterosclerosis. Los datos sugieren que, en este modelo murino, el consumo sostenido de bebidas cola durante las etapas tempranas de la vida puede acelerar el agravamiento del daño aterosclerótico en etapas más tardías.

Cola Beverages Accelerate Growth of the Atherosclerotic Plaque in ApoE-/- Mice Introduction Unhealthy eating habits during childhood and youth have been suggested as predisposing factors to atherosclerotic complications later in life. The growing consumption of cola beverages in recent decades has been associated with the development of obesity and increased incidence of atherosclerosis and cardiovascular disease. We also know that there is a correspondence between the consumption of these beverages and the different stages of life, being higher in children, adolescents and young adults. Objective This study evaluates the effect of cola beverage consumption on atherosclerosis. Methods ApoE-/- mice (8 week-old) were randomized into 3 groups according to free access to water (W), sucrose sweetened carbonated cola drink (C) or aspartame-acesulfame K sweetened carbonated 'light' cola drink (L). At 8 weeks cola beverages were switched to water. The mice were sequentially euthanized: before treatment (8 week old mice) and after treatment discontinuation (20, 24, and 30 week old mice). The ascending aorta and the liver were removed. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Hepatic inflammation was assessed according to the NASH scale. Results Plaque/media-ratio varied according to drink treatment (F2,54=3.433, p <0.04) and age (F4,54=5.009, p <0.03) and was higher in the C and L groups (p <0.05 at 16 and 20 weeks, p <0.01 at 24 and 30 weeks). Hepatic parenchymal inflammation (F2,9=13.29, p <0.002) and portal inflammation (F2,9 =6.30, p <0.02) varied fivefold and twofold in contrast to steatosis and hepatocellular damage which remained unchanged throughout the study.Natural evolution of atherosclerosis in ApoE-/- mice (W group) evidenced acceleration of plaque growth in parallel with a rapid increase in hepatic inflammation around week 20 of age. Conclusions Cola beverage consumption in 8-16 week old ApoE-/- mice accelerated atherosclerosis progression. Data suggest that, in this murine model, sustained cola consumption at early stages of life may predispose to atherosclerosis progression later in life.