The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis.

BACKGROUND AND AIMS: To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations. METHODS: Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software. RESULTS: 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215-Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL. 3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC. CONCLUSIONS: The pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.

Polimorfismos de los genes LEP , LDLR , APOA4 y sus relaciones con el sobrepeso, la obesidad y el riesgo de enfermedades crónicas en adultos del estado Sucre, Venezuela / LEP , LDLR and APOA4 gene polymorphisms and their relationship with the risk of overweight, obesity and chronic diseases in adults of the State of Sucre, Venezuela

Introducción. La prevalencia del sobrepeso, la obesidad y algunas enfermedades crónicas no transmisibles ha aumentado; sus causas pueden ser genéticas, epigenéticas o ambientales, por lo cual es importante evaluar la variabilidad en estas interacciones. Objetivo. Analizar las relaciones entre nueve polimorfismos de nucleótido simple de los genes LEP (rs2167270), LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) y APOA4 (rs5095, rs675, rs5110), y los fenotipos asociados al sobrepeso, la obesidad y otras enfermedades concomitantes. Materiales y métodos. Se evaluaron parámetros clínicos y antropométricos en 144 sujetos del estado Sucre, Venezuela, 76 hombres y 68 mujeres , con medias de edad de 29,93±8,29 y 32,49±11,15 años, respectivamente. Se hizo la genotipificación de los polimorfismos seleccionados mediante enzimas de restricción; se estudiaron las asociaciones entre genotipo y riesgo, y se compararon los promedios de las medidas antropométricas y bioquímicas previamente ajustadas a variables biológicas y ambientales. Resultados. Según el índice de masa corporal (IMC), el 38,9 % de los individuos tenía sobrepeso (25=IMC=29,9 kg/m 2 ) y el 20,1 %, obesidad (IMC=30 kg/m 2 ) . Las frecuencias genotípicas y alélicas de los grupos con un índice de masa corporal normal y uno alto (sobrepeso y obesidad) resultaron similares. Solo se encontró asociación entre el genotipo ancestral A/A del rs5742911 y el riesgo alto por los niveles de la lipoproteína de alta densidad o colesterol HDL (OR=2,944, IC 95% 1,446-5,996; p=0,003). La diferencia entre los promedios corregidos de colesterol HDL para los genotipos del rs5742911 resultó significativa (p=0,005) (A/A: 41,50±14,81 mg/dl; A/G: 45,00±12,07 mg/dl; G/G: 47,17±9,43 mg/dl). Conclusión. En la mayoría de las variantes genéticas estudiadas, se registró la asociación con el sobrepeso y la obesidad de los genotipos ancestrales, aunque sin ser significativa. El polimorfismo rs5742911 podría resultar útil como indicador del riesgo de enfermedades crónicas.

Introduction: Overweight, obesity and some chronic diseases have become more prevalent recently. It is well known that their causes may be genetic, epigenetic, environmental, or a mixture of these. Objective: To analyze the relationship between nine single nucleotide polymorphisms of genes LEP (rs2167270) , LDLR (rs885765, rs688, rs5925, rs55903358, rs5742911) and APOA4 (rs5095, rs675, rs5110) with obesity-related phenotypes and other comorbidities. Material and methods: We recruited 144 adults (76 males and 68 females, with average ages of 29.93±8.29 and 32.49±11.15 years, respectively) in the State of Sucre, Venezuela. Clinical and anthropometric parameters were obtained. Genotype-risk associations were studied. We then compared the averages registered for anthropometric and biochemical variables previously adjusted for biological and environmental factors. Results: According to the body mass index, 38.9% of the individuals in the sample were overweight (25=BMI=29.9 kg/m 2 ) and 20.1% were obese (BMI=30 kg/m 2 ). Genotype and allele frequencies did not differ statistically for groups with normal and high body mass index (overweight plus obesity). The association between LDLR rs5742911 ancestral genotype A/A and high risk condition related to HDL-cholesterol was the only one found to be significant (OR=2.944, 95% CI: 1.446-5.996; p=0.003). The difference in adjusted mean HDL-cholesterol for LDLR rs5742911 genotypes was statistically significant (p=0.005) (A/A: 41.50±14.81 mg/dL; A/G: 45.00±12.07 mg/dL; G/G: 47.17±9.43 mg/dL). Conclusions: For most of the genetic variants studied, there was an association with the presence of overweight and obesity among ancestral genotype carriers, although this was not statistically significant. The rs5742911 polymorphism may be useful as an indicator of a risk of chronic diseases.

Lipoprotein (a): Structure, Pathophysiology and Clinical Implications / Lipoproteína (a): Estrutura, Metabolismo, Fisiopatologia e Implicações Clínicas

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.

Impacto de la apolipoproteína A5 en el riesgo cardiovascular: Modulaciones genéticas y ambientales / Impact of apolipoprotein A5 on cardiovascular risk: Genetic and environmental modulation

Triglyceride concentrations are an independent risk factor for coronary heart disease. Apolipoprotein A5 gene (APOA5) has an important role determining triglyceride metabolism and it is a potential cardiovascular risk. However the mechanisms for these actions are not well-known. Despite the different allelic frequency of its major polymorphisms in different populations, multiple studies have shown consistent associations between these variants and fasting triglycerides. Variations in the APOA5 gene have also been associated with postprandial triglycerides, as well as with different sizes of lipoproteins and other markers. Moreover, some of the APOA5 gene variants have been associated with ischemic heart disease, stroke, and carotid intima media thickness, although the references on this issue are scanty and contradictory. This may be due to the presence of gene-environment interactions that have been poorly studied until now. Among the few studies that have examined the infuence of environmental factors on possible genetic variations, the most important are those that contemplate possible gene-diet interactions. However, the evidence is still scarce and more research is required in the feld of nutrigenomics. To understand the impact of this gene on cardiovascular disease, we review the genetic functionality and variability of APOA5, its associations with intermediate and fnal phenotypes and gene-environment interactions detected.

Polimorfismos genéticos de APOA5 se asocian a hipertrigliceridemia e hiperglicemia en individuos chilenos con enfermedad coronaria y controles / Genetic polymorphisms of APOA5 are associated with hypertriglyceridemia and hyperglycemia in Chilean subjects with coronary artery disease and controls

Introducción: Diversas variantes genéticas han sido relacionadas al desarrollo de enfermedad coronaria y/o sus factores de riesgo; entre ellas, los polimorfismos S19W y -1131T>C del gen que codifica para la apolipoproteína A5 (APOA5). Así, el objetivo del presente estudio fue investigar la posible asociación entre las variantes S19W y -1131T>C del gen APOA5 y enfermedad coronaria en individuos chilenos. Métodos: Se evaluaron 425 sujetos adultos, no relacionados; 209 pacientes con enfermedad coronaria (EC) comprobada por angiografía (estenosis→ 70 por ciento), con edades entre 33 y 74 años, y 216 individuos controles (30 a 68 años). La genotipificación de los polimorfismos S19Wy -1131T>C del gen APOA5 fue realizada mediante la técnica de PCR-RFLP Resultados: La distribución de los genotipos para el polimorfismo S19W del gen APOA5 en el grupo casos (SS: 80 por ciento, SW: 19 por ciento y WW: 1 por ciento) y en el grupo control (SS: 82 por ciento, SW: 17 por ciento y WW: 1 por ciento) fue semejante (p=NS). La distribución genotípica para el polimorfismo -1131T>C en pacientes con EC (TT: 56 por ciento, TC: 37 por ciento, y CC: 7 por ciento) y controles (TT: 63 por ciento, TC: 30 por ciento y CC: 7 por ciento) fue similar (p=NS). Las ORs relacionadas a los alelos mutados 19W (1.12; I.C.95 por ciento, 0.72- 1.74, p=NS)y-1131C (1.19; I.C.95 por ciento,, 0.87- 1.63, p=NS), confirman la ausencia de asociación. Por otro lado, las concentraciones de triglicéridos y glucosa en ayunas fueron significativamente más elevadas en los sujetos portadores de los alelos 19Wy -1131C, tanto en casos como en controles (p<0.05). Conclusión: La asociación observada entre las variantes genéticas de APOA5 y las altas concentraciones séricas de triglicéridos y glucosa, en ambos grupos, sugiere que estos polimorfismos podrían contribuir al desarrollo de la dislipidemia diabética; un reconocido factor de riesgo para enfermedad arterial coronaria.

Background: Several genetic variants have been linked to the development of coronary heart disease and/or their risk factors, including the S19Wand-1131T> C polymorphisms of the gene that encodes apolipoprotein A5 (APOA5). Thus, the objective of this study was to investigate the possible association between S19W and -1131T>C genetic variants ofAPOA5 and coronary disease in Chilean individuals. Methods: We evaluated 425 not related subjects; 209 patients with coronary artery disease (CAD) confirmed by angiography (stenosis→ 70 percent,), aged between 33 and 74 years, and 216 control individuals (30 to 68 years). The genotyping of S19W and -1131T>C polymorphisms of APOA5 gene was evaluated by PCR-RFLP. Results: The genotype distribution of S19W polymorphism of APOA5 gene in CAD patients (SS: 80 percent,, SW: 19 percent, WW: 1 percent>) and controls (SS: 82 percent,, SW: 17 percent, WW: 1 percent>) was similar (p = NS). In the same way the genotype distribution of-1131T>C genetic variant in CAD subjects (TT: 56 percent,, TC: 37 percent,, and CC: 7 percent>) and controls (TT: 63 percent,, TC: 30 percent, and CC: 7 percent) was equivalent (p = NS). The Odds ratios related to the mutant alleles 19W (1.12, 95 percent, Cl, 0.72 - 1.74, p = NS) and -1131C (1.19, 95 percent, Cl, 0.87 -1.63, p = NS) confirms the absence of association. On the other hand, the triglycerides and fasting glucose concentrations were significantly higher in subjects carrying the alleles 19W and -1131C, in both groups, CAD patients and controls (p <0.05). Conclusion: The observed association between genetic variants of APOA5 and higher serum levels of triglycerides and glucose, in both groups, suggesting that these polymorphisms could be contribute to the development of diabetic dyslipidemia, a known risk factor for coronary artery disease.

El polimorfismo -1131 T>C del promotor del gen de la apolipoproteína A5 altera la unión de NRF2 (nuclear respiratory factor-2) y disminuye la actividad del promotor / -1131 T>C polymorphism of the apolipoprotein A5 gene promoter alters the binding of NRF2 (nuclear respiratory factor 2) and decreases promoter activity

Introducción. El papel que desempeñan los triglicéridos (TG) ingeridos en la dieta en la aparición de aterosclerosis es controvertido. Sin embargo, recientemente se ha descrito que los valores de TG en estado posprandial son un factor de riesgo independiente para la aparición de esta enfermedad. Recientemente, se ha identificado la apolipoproteína (Apo) AV como una proteína clave en la regulación del metabolismo de los TG. El polimorfismo ¿1131 T>C del gen de la ApoA5 se ha asociado con cambios en los valores plasmáticos de TG y de ApoAV. El objetivo de este trabajo fue determinar el papel del polimorfismo ¿1131 T>C en la expresión del gen ApoA5. Material y métodos. Con el fin de estudiar la influencia de este single nucleotide polymorphisms (SNP) en la expresión de este promotor, se han utilizado construcciones de genes reporteros de ambos alelos. Mediante experimentos de retardo en gel se demostró que este polimorfismo también altera la secuencia de unión a NRF-2. Conclusiones. Nuestros resultados indicaron que la actividad del promotor de ApoA5 que porta la variante T del SNP ¿1131 T>C es mayor que la del promotor que lleva el alelo C. Además, este cambio de nucleótido se traduce en un cambio de afinidad proteínas-ácido desoxirribonucleico. Estos resultados indican que un cambio en la actividad del promotor del gen ApoA5 podría ser la causa del incremento de los valores plasmáticos de TG asociados con el alelo C (AU)

Introduction. Postprandial triglycerides (TG) have been established as an independent risk factor for atherosclerosis, even though the role of fasting TG in the pathogenesis of this disease remains controversial. Recently, apolipoprotein AV (ApoAV) has been identified as a key player in TG metabolism. The ¿1131 T>C polymorphism in the ApoA5 gene promoter has been associated with changes in plasma triglyceride and ApoAV levels. Our objective was the functional analysis of the SNP ¿1131 T>C located on ApoA5 promoter to clarify his effect on ApoA5 expression. Material and methods. In order to test if this SNP influences promoter function, we have performed reporter gene assays. Our results indicated that the promoter carrying the T allele is stronger than its C- allele variant. Additionally electrophoretic ¿ mobility shift assays showed that the variant also produces a change in a NRF-2 binding site. Conclusions. Together, these results suggest that a change in the activity of ApoA5 promoter could be responsible for the increases in plasma TG levels associated with the C allele (AU)

Lipoproteína A, "el colesterol malísimo" / A lipoprotein

La hiperlipidemia por lipoproteína a -LDL más apo a- es un factor de riesgo vascular aterotrombótico, familiar, independiente y poderoso, llamativamente desconsiderado. Este trabajo tiene como objetivo su mejor diagnóstico y tratamiento.

La grasa saturada en la dieta disminuye la expresión hepática de APOA5 en ratones deficientes en apo E / Saturated fat from diet downregulates APOA5 hepatic expression in apo E-deficient mice

Introducción. En el desarrollo de la arteriosclerosis intervienen numerosos factores; en especial la edad, la dieta y la hiperlipidemia. La apolipoproteína (apo) A-V desempeña un papel destacado en el control del metabolismo lipídico. Nuestro objetivo es estudiar en ratones hiperlipémicos el efecto que la grasa de la dieta tiene en la expresión hepática del gen de la apo A-V (APOA5) y su relación con el desarrollo de la arteriosclerosis y sus factores de riesgo. Material y métodos. Utilizamos 72 ratones knock-out para el gen de la apo E (KO-APOE) separados en 3 grupos (n = 24): los que recibían dieta convencional de ratón o dieta rica en grasa saturada (20% aceite de palma) sola o suplementada con 0,25% de colesterol. Las muestras se tomaron a las 16, 24 y 32 semanas de edad. Las determinaciones analíticas incluyeron parámetros lipídicos e inflamatorios, la superficie de lesión arteriosclerótica en la aorta y la expresión de APOA5 en hígado. Resultados. La ingesta de dieta rica en grasa saturada disminuye un 48% (p = 0,001) de media la expresión hepática de APOA5 y la suplementación con colesterol revierte este efecto. Estos efectos se observaron a las diferentes edades de los ratones. La expresión hepática de APOA5 aumenta significativamente (p < 0,0001) en función de la edad, el número de lesiones arterioscleróticas en la aorta y el grado de inflamación en los ratones. Conclusiones. La grasa saturada de la dieta disminuye significativamente la expresión hepática de APOA5, que a su vez aumenta con la edad a todas las dietas suministradas y se correlaciona con el área ateromatosa y el estado inflamatorio (AU)

Introduction. Many factors are involved in atherosclerosis development, especially age, diet and hyperlipidemia. Apolipoprotein (apo) A-V plays a key role in the control of lipid metabolism. The aim of this study was to determine the effect of dietary fat intake on hepatic expression of the apo A-V gene (APOA5) in hyperlipidemic mice and its association with risk factors for atherosclerosis and atherosclerosis development. Material and methods. We used 72 knock-out mice for the apo E gene (KO-APOE) divided in three groups (n=24) that received a chow diet, a diet rich in saturated fat (20% palm oil) alone, or a diet supplemented with 0.25% of cholesterol. Samples were obtained at 16, 24, and 32 weeks. Laboratory determinations included lipid and inflammatory parameters, area of atherosclerotic lesions in the aorta, and APOA5 expression in the liver. Results. Intake of a saturated fat-rich diet reduced mean hepatic expression of APOA5 by 48% (P=0.001), while cholesterol supplementation reversed this effect. These effects were found at the different ages of mice. Hepatic APOA5 expression significantly increased (P=0.001), depending on age, the number of atherosclerotic lesions in the aorta, and the degree of inflammation in these mice. Conclusions. Saturated dietary fat significantly downregulates hepatic APOA5 expression, which also increases with age, in all the diets administered and correlates with atheromatous area and inflammatory status (AU)

DNA Polymorphisms and Haplotypes of Apolipoprotein A5's Attribution to the Plasma Triglyceride Levels in Koreans

PURPOSE: Recent studies using human and mice reported that apolipoprotein A-V (APOA5) gene plays an important role in controlling triglyceride (TG) concentrations. The purpose of the present study was to investigate the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in the APOA5 gene and TG in subjects and to search for possible associations of the APOA5 gene variants and common haplotypes with hypertriglyceridemia (HTG). MATERIALS AND METHODS: We examined the case-control subjects including 100 HTG patients and 243 unrelated healthy control. The genes were screened for SNPs by direct sequencing in 48 genetically unrelated individuals. Six SNPs (-1390C>T, -1020G>A, -3A>G, V150M, G182C and 1259T>C) were genotyped in case and control populations. RESULTS: In this study, our results indicated a strong association between APOA5 SNP -3A>G and G182C and elevated TG levels (p<0.001). Analysis of the SNPs from APOA5 gene has identified major haplotype showing very strong association with HTG, CGGGTT (p<0.001). Likelihood ratio test (LRT) of these six SNPs revealed that haplotypes were strong independent predictors of HTG (p<0.001). Haplotype-trend logistic regression (HTR) analysis revealed a significant association between the CGGGGC (haplotype 2) and CGGGTT (haplotype 4) and HTG (OR=2.48, 95% CI=1.06-5.76 and OR=8.54, 95% CI=2.66-27.42, respectively). CONCLUSION: We confirm that the APOA5 variants are associated with triglyceride levels and the haplotype may be strong independent predictors of HTG among Koreans.

APOA1/C3/A4 gene cluster variability and lipid levels in Brazilian children

Genetic studies have suggested that polymorphisms of genes coding for apolipoproteins are significant determinants of serum lipoprotein and lipid levels in adults. However, only a few studies have investigated the association of these polymorphisms in children. Therefore, in the present investigation we studied the distribution of APOA1 -75 G>A, +83 C>T, APOC3 -482 C>T, -455 T>C and 3238 C>G, and APOA4 Q360H and T347S polymorphisms and their influence on plasma lipoprotein levels in children from a Brazilian northeastern admixed population. The seven polymorphic sites were genotyped in 414 children aged 5 to 15 years (mean 8.9 ± 2.9). The genotypes of the seven polymorphic sites were assessed by PCR-RFLP methods. The frequencies of the less common alleles were, in general, intermediate among parental populations, as expected. Strong linkage disequilibrium was detected between polymorphisms at the APOA1, APOC3 and APOA4 loci in this admixed population sample. Overall the genotype effects seen in adults were weaker or absent in children. The APOC3/-455 and APOA4 T347S variants showed significant effects on HDL cholesterol in girls (P = 0.033 and P = 0.016, respectively). Significantly higher plasma total (P = 0.003) and LDL cholesterol (P = 0.004) levels were observed in boys who were carriers of the 3238G allele at the APOC3/3238 C>G site. These results disclosed an overall absence of associations between these polymorphisms and lipids in children. This finding is not unexpected because expression of the effect of these polymorphisms might depend on the interaction with environmental variables both internal and external to the individual.

Aspectos diagnósticos y funcionales de las Apolipoproteínas E y A-IV / Apolipoprotein E and A-IV diagnostic and functional aspects

En el presente trabajo se analizaron dos aspectos distintos del metabolismo lipoproteico. En el primero, en un estudio bioquímico clínico, se presentó un método rápido y simple de determinación de los polimorfismos de la apoE. La utilidad clínica de conocer el genotipo apoE fue evaluada correlacionando las isoformas de apoE con el espesor carotideo estimado con ecografía de ultrasonido. Los resultados mostraron que el genotipo apoE4 ejerce un efecto sobre la aterosclerosis carotídea, efecto que puede ser detectado antes que cualquier otro síntoma clínico. En la segunda parte de éste trabajo se ha analizado el metabolismo lipoproteico en ratones transgénicos expresando la apolipoproteína A-IV (apoA-IV) humana. Los resultados muestran que la apoA-IV tiene un rol pleiotrópico en el organismo, relacionado con la protección contra la aterosclerosis y con la regulación de la secreción gástrica

Aspectos diagnósticos y funcionales de las Apolipoproteínas E y A-IV / Apolipoprotein E and A-IV diagnostic and functional aspects

En el presente trabajo se analizaron dos aspectos distintos del metabolismo lipoproteico. En el primero, en un estudio bioquímico clínico, se presentó un método rápido y simple de determinación de los polimorfismos de la apoE. La utilidad clínica de conocer el genotipo apoE fue evaluada correlacionando las isoformas de apoE con el espesor carotideo estimado con ecografía de ultrasonido. Los resultados mostraron que el genotipo apoE4 ejerce un efecto sobre la aterosclerosis carotídea, efecto que puede ser detectado antes que cualquier otro síntoma clínico. En la segunda parte de éste trabajo se ha analizado el metabolismo lipoproteico en ratones transgénicos expresando la apolipoproteína A-IV (apoA-IV) humana. Los resultados muestran que la apoA-IV tiene un rol pleiotrópico en el organismo, relacionado con la protección contra la aterosclerosis y con la regulación de la secreción gástrica (AU)

Genetic variation of the Apo Al-CIII-AIV gene cluster in hypertriglyceridemic patients with chronic renal failure undergoing hemodialysis

Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.

Genetic variation of the Apo Al-CIII-AIV gene cluster in hypertriglyceridemic patients with chronic renal failure undergoing hemodialysis

Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p>0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF.