ABSTRACT
BACKGROUND: To study whether the Apolipoprotein A-I (apo A-I) promoter region gene polymorphism produces changes in the lipid profile of heart transplant recipients. METHODS: One hundred and three heart transplant recipients (93 men and 10 women, with a mean age of 47 +/- 13 yr) receiving triple immunosuppressive therapy were submitted to a genetic study of the apo A-I gene promoter region. Anthropometric and analytical data, including lipid profile, arterial blood pressure, were collected prior to transplantation and 3, 6, 12, and 24 months after transplantation. RESULTS: Sixty-three subjects had the GG genotype and 40 the GA genotype. Carriers of the GA genotype had higher triglyceride levels at 6 months and 2 yr (2.50 +/- 1.20 versus 1.93 +/- 0.98 mmol/L and 2.46 +/- 1.58 versus 1.60 +/- 0.68 mmol/L, respectively, p < 0.001), and a greater rise in LDL-cholesterol at 1 yr than the GG subjects (4.57 +/- 1.16 versus 4.16 +/- 1.18 mmol/L, p < 0.05). Multiple regression analyses showed that genetic variants at the apo A-I promoter region are responsible for 11% of the variability in triglyceride levels at 6 months (p = 0.005). CONCLUSIONS: The GA genotype of the apo A-I promoter region produces a greater rise in plasma triglyceride and LDL-cholesterol levels in heart transplant patients.
Subject(s)
Apolipoprotein A-I/genetics , Heart Transplantation , Hyperlipidemias/blood , Hyperlipidemias/genetics , Polymorphism, Genetic , Data Interpretation, Statistical , Female , Genotype , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Promoter Regions, Genetic , Prospective StudiesABSTRACT
BACKGROUND: There is considerable interindividual variability in the postprandial lipid response to a fat-rich meal, and genetic factors have been considered to account for some of these effects. We previously showed that the G-A mutation 5' to the apolipoprotein (apo) A-I gene was significantly associated with the LDL-cholesterol response to diet. OBJECTIVE: We evaluated whether this effect is mediated by mechanisms involving postprandial lipoprotein metabolism. DESIGN: Twenty-eight G/G and 23 G/A healthy male subjects, homozygotes for the apo E3 allele, were subjected to a vitamin A fat-loading test. Blood was drawn at time 0 and every hour for 11 h. RESULTS: There was a significant postprandial decrease in plasma cholesterol, LDL cholesterol, and apo B in G/G subjects but not in G/A subjects. A greater postprandial response in large triacylglycerol-rich lipoproteins (TRLs) and a smaller postprandial response in large TRL apo A-IV was observed in G/A than in G/G subjects. Retinyl palmitate in large and small TRL concentrations was similar for both genotypes. No significant genotype effects were detected for triacylglycerol concentrations in plasma, small TRL fraction, and apo A-I and HDL-cholesterol concentrations. CONCLUSION: Our data suggest that the G-A mutation affects the LDL-cholesterol response to diet by mechanisms involving postprandial lipoprotein cholesterol metabolism.
Subject(s)
Apolipoprotein A-I/genetics , Apolipoproteins B/blood , Cholesterol/blood , Lipoproteins/metabolism , Postprandial Period , Vitamin A/pharmacology , Adult , Apolipoprotein B-100 , Apolipoprotein B-48 , Genotype , Humans , Middle Aged , Polymerase Chain Reaction , Vitamin A/administration & dosageABSTRACT
Fundamento: Numerosos paneles de expertos, en especial de países anglosajones, recomiendan la dieta pobre en grasa para la prevención de enfermedades cardiovasculares. Sin embargo, la tasa de muerte por cardiopatía isquémica es baja en los países del área mediterránea, lo que puede ser debido al alto porcentaje de grasa monoinsaturada proporcionada por el aceite de oliva en la dieta. Por ello hemos comparado el efecto de ambas dietas sobre la susceptibilidad in vitro a la oxidación de las lipoproteínas de baja densidad (LDL), pieza clave en el inicio y desarrollo de la arteriosclerosis. Sujetos y métodos: Cuarenta y un sujetos varones sanos normolipémicos fueron sometidos a tres períodos de dieta, de 4 semanas de duración cada uno, consistentes en una dieta rica en grasa saturada (SAT: 38 por ciento grasa, 20 por ciento saturada), otra pobre en grasa (NCEP-I: 28 por ciento grasa, 10 por ciento saturada) y una dieta medi-terránea (38 por ciento grasa, 22 por ciento de grasa monoinsaturada). Al final de cada período dietético se determinaron las concentraciones plasmáticas de colesterol total, cLDL, cHDL, triglicéridos, apoproteínas A-I y B, *-tocoferol y la susceptibilidad a la oxidación de las LDL in vitro. Resultados: Ambas dietas hipolipemiantes produjeron un descenso significativo de las concentraciones plasmáticas de colesterol total, cLDL y apo B, mientras que sólo la dieta NCEP-I disminuyó el cHDL. La sustitución de una dieta rica en grasa saturada o de una dieta rica en hidratos de carbono por una dieta mediterránea aumentó la resistencia a la oxidación de las LDL al prolongarse el tiempo de latencia (p < 0,038) e inducir un descenso (p < 0,001) en la tasa de progresión de la curva de cinética de oxidación de las LDL. Conclusión: Nuestros resultados indican que el consumo de una dieta mediterránea rica en aceite de oliva, además de mejorar el índice aterogénico (colesterol total/cHDL), aumenta la resistencia a la oxidación de las LDL en comparación con la dieta pobre en grasa. Ello nos hace aconsejar el modelo de dieta mediterránea para la prevención de las enfermedades cardiovasculares. (AU)
Subject(s)
Middle Aged , Adult , Aged, 80 and over , Aged , Male , Female , Humans , Plant Oils , Diet , Dietary Fats , Sensitivity and Specificity , Biomarkers, Tumor , Biomarkers , Mediterranean Region , Diet, Fat-Restricted , Nuclear Proteins , Oxidation-Reduction , Prospective Studies , Antigens, Nuclear , Cardiovascular Diseases , Dietary Fats, Unsaturated , Antigens, Neoplasm , Urinary Bladder Neoplasms , Keratins , Cholesterol, LDL , Cholesterol, HDLABSTRACT
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