Factor VII polymorphisms influence the plasma response to diets with different fat content, in a healthy Caucasian population.

UNLABELLED: To determine the influence of the factor VII gene polymorphisms, R353Q and 5'F7, on factor VII Ag plasma levels after the consumption of diets with different fat contents. METHODS: 59 healthy individuals (42 RR, 16 RQ, 1 QQ at the R353Q and 46 A1A1, 13 A1A2 at the 5'F7) consumed 3 diets during 4-weeks each: a Saturated diet (SAT) enriched in saturated fatty acid (SFA) (38% fat, 20% SFA), followed by a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a Mediterranean diet (MEDIT) enriched in monounsaturated fatty acid (MUFA) (38% fat, 22% MUFA) following a randomized crossover design. Plasma lipids and FVII Ag plasma levels were determined at the end of each dietary period. RESULTS: After a SAT diet, RR homozygotes had greater concentrations of FVII Ag compared with MEDIT and CHO diets than did carriers of the minority Q allele (82.76 +/- 1.3 vs. 75.02 +/- 2.4, p = 0.001). The 5'F7 polymorphism behaved in a similar fashion (A1A1 81.98 +/- 1.4 vs. A1A2 75.37 +/- 2.4, p = 0.026). CONCLUSIONS: Our data show that carriers of the RR and/or A1A1 genotype present higher FVII Ag levels after the consumption of a SAT diet compared with the MEDIT and CHO rich diets.

The APOB -516C/T polymorphism has no effect on lipid and apolipoprotein response following changes in dietary fat intake in a healthy population.

Our goal was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter modifies the lipid response to changes in the amount and quality of dietary fat. We studied 97 young healthy volunteers (70 males and 27 females), 62 homozygotes for the -516C allele (C/C) (47 males and 15 females), 34 heterozygotes for the -516T allele (C/T) (22 males and 12 females) and one male homozygote for the -516T allele (T/T). Subjects consumed three different diets in successive 4-week dietary periods. During the first 28 days, all subjects consumed a saturated fatty acid (SFA)-rich diet (38% fat and 20% SFA). Then, using a randomized crossover design, subjects were assigned a carbohydrate (CHO)-rich diet (30% fat and 55% carbohydrate) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat and 22% MUFA). At the end of each dietary period, plasma concentrations of triacylglycerols and of total, LDL, and HDL cholesterol were measured. No differences in plasma lipid and apolipoprotein response were found after changes in dietary fat intake in relation to the -516C/T polymorphism in our study population. In conclusion, our data suggest that the APOB -516C/T polymorphism has no effect on the lipid profile after changes in dietary fat intake in a healthy population.

[Clinical significance of increased serum ferritin levels]. / Significado clínico de los valores elevados de ferritina sérica.

BACKGROUND AND OBJECTIVE: We aimed to determine the diagnostic alternatives indicated by serum ferritin levels (2000 ng/ml, and to establish the clinical processes associated with very high levels (5000-10 000 ng/ml). PATIENTS AND METHOD: We retrospectively analyzed cases with serum levels of ferritin serum equal to or greater than 2000 ng/ml between March 2000 and November 2001. Data were obtained from the laboratory's computerized database. Patients' medical records were reviewed by means of a protocol which established the clinical conditions associated with these serum ferritin values. RESULTS: The study involved 135 patients with ferritin levels equal to or greater than 2000 ng/ml. Clinical syndromes included hematological diseases (45.9%), liver diseases (23%), chronic renal failure (17.78%), neoplastic diseases (10.4%), systemic inflammatory diseases (7.4%), chronic transfusions (7.4%), and non-HIV systemic infections (5.9%). Syndromes which are not usually associated with extreme serum ferritin levels were identified in 3.7% of the patients. The highest concentrations were seen in the systemic inflammatory disease group: 5856 (2492) ng/ml. Within this group, four patients with adult onset Still's disease (AOSD) displayed the highest mean ferritin levels: 11 322 (5474) ng/ml. CONCLUSIONS: Elevated serum ferritin levels act as a non-specific marker for a large number of disorders. In certain inflammatory diseases such as adult onset Still's disease (AOSD), this finding may be an important tool.

The influence of the apolipoprotein E gene promoter (-219G/ T) polymorphism on postprandial lipoprotein metabolism in young normolipemic males.

The apolipoprotein E (apoE) gene promoter (-219G/T) polymorphism has been associated with increased risk of myocardial infarction, premature coronary heart disease, and decreased plasma apoE concentrations. We examined whether the -219G/T polymorphism could modify the postprandial response of triacylglycerol-rich lipoproteins (TRLs). Fifty-one healthy apoE 3/3 male volunteers (14GG, 29GT, and 8TT) were given a vitamin A fat-loading test consisting of 1 g of fat/kg body weight and 60,000 IU of vitamin A per m2 of body surface area. Blood samples were taken at time 0 and every hour until the sixth hour, and every 2 hours and 30 minutes until the eleventh hour. Cholesterol, triacylglycerols (TGs), and apoE were determined in plasma; and cholesterol, TG, apoB-100, apoB-48, and retinyl palmitate (RP) were analyzed in lipoprotein fractions. Postprandial lipemia data revealed that subjects with the -219TT genotype had a higher postprandial response of large TRL-cholesterol (P < 0.03), large TRL-triacylglycerols (P < 0.001), large TRL-RP (P < 0.004), and small TRL-apoB-48 (P < 0.03) than carriers of the -219G allele. Moreover, the -219TT subjects had the lowest postprandial levels of serum apoE (P < 0.05). In conclusion, the -219G/T polymorphism may influence TRL metabolism during the postprandial period, thus prolonging postprandial lipemia in subjects with the TT genotype.

Polymorphism exon 1 variant at the locus of the scavenger receptor class B type I gene: influence on plasma LDL cholesterol in healthy subjects during the consumption of diets with different fat contents.

BACKGROUND: The association between polymorphisms in the scavenger receptor class B type I (SRB-I) gene and variations in basal plasma concentrations of cholesterol in humans has recently been described. OBJECTIVE: The objective of the study was to determine whether the exon 1 variant (G-->A) at the SRB-I gene is associated with the lipid response to the content and quality of dietary fat in healthy subjects. DESIGN: We studied 97 healthy volunteers with exon 1 polymorphism [65 homozygous for allele 1 (1/1) and 32 heterozygous for allele 2 (1/2)]. Both groups consumed 3 diets lasting 4 wk each. The first was a saturated fatty acid (SFA)-rich diet (38% fat, 20% SFA), which was followed by a carbohydrate (Cho)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA), olive oil-rich diet (38% fat, 22% MUFA) according to a randomized crossover design. At the end of each dietary period, plasma concentrations of triacylglycerol and of total, LDL, and HDL cholesterol were measured. RESULTS: Carriers of the 1/2 genotype had a trend toward higher concentrations of LDL cholesterol (P < 0.11) after the SFA-rich diet than did those who were homozygous for 1/1. Carriers of the mutation showed a significantly greater (P = 0.007) decrease in LDL-cholesterol concentrations (-23%) in changing from an SFA-rich diet to a Cho-rich diet than did noncarriers of the mutation (-16%). CONCLUSION: Carriers of the minority allele, 1/2, are more susceptible to the presence of SFA in the diet because of a greater increase in LDL cholesterol.

[Response degree of cholesterol LDL to feeding in males with hypercholesterolemia according to baseline value]. / Grado de respuesta del colesterol LDL a la alimentación en varones con hipercolesterolemia según sus valores basales.

BACKGROUND: The response of plasma cholesterol to diet is modulated by endogenous and exogenous factors such as body mass, tobacco consumption, gender and the genetic background. Our purpose was to know whether the response degree depends on the concentration of cholesterol prior to the intervention and whether several polymorphisms modulating the cholesterol response to diet are actually involved in such response. PATIENTS AND METHOD: Seventy two males with hypercholesterolemia were administered three different 4-weeks duration diets. The first one was a saturated fat-enriched (SAT) diet. Then, in a randomized and crossed manner, subjects were categorized in two groups: one group received a diet with low fat but high complex carbohydrates contents (HCO); the another group received a monounsaturated fat-enriched diet (Mediterranean diet). In the third period, we inverted the diets of the previous period. We determined the prevalent genotypes of the following apoproteins: E, CIII, A-IV, A-I, B, A-IV 360. RESULTS: The diet with low fat contents and the Mediterranean diet led to a significant decrease of total cholesterol, LDL-c and HDL-c. Those at the upper LDL-c tertile, after the SAT diet, were found to have statistically significant greater decreases (absolute and relative values) with the Mediterranean and HCO diet. In the multivariate analysis, the only variable with an effect on the modification of LDL-c, after shifting a SAT to any hypolipidemic diet, were the levels of LDL-c at the end of a SAT diet. The allelic frequency of different apoproteins in the hyper-respondent group was not different from that in the hypo-respondent group (response displayed when going from a SAT period to any hypolipidemic diet). CONCLUSIONS: The decrease of LDL-c observed with hypolipidemic diets (low in fat contents or Mediterranean) was more significant in those individuals with hypercholesterolemia who had higher levels of LDL-c at the onset.

Grado de respuesta del colesterol LDL a la alimentación en varones con hipercolesterolemia según sus valores basales / Response degree of cholesterol LDL to feeding in males with hypercholesterolemia according to baseline value

FUNDAMENTO: La respuesta del colesterol plasmático a la alimentación está modulada por factores endógenos y exógenos, tales como el índice de masa corporal, el consumo de tabaco, el género y el sustrato genético. El propósito de nuestro trabajo fue conocer si la magnitud de la respuesta depende también del valor de colesterol previo a la intervención, y si en dicha respuesta influye la presencia de varios polimorfismos prevalentes, ya conocidos como moduladores de cambios en la respuesta del colesterol a la alimentación. PACIENTES Y MÉTODO: Setenta y dos varones con hipercolesterolemia recibieron tres dietas de 4 semanas de duración cada una. La primera fue rica en grasa saturada (SAT). Tras ésta, y de forma aleatoria y cruzada, se dividieron en dos grupos: uno recibió una dieta pobre en grasa y rica en hidratos de carbono complejos (HCO), el otro una rica en grasa monoinsaturada (dieta mediterránea). Durante el tercer período se invirtieron las dietas de la fase anterior. Determinamos los genotipos prevalentes de las apoproteínas E, C-III, A-IV, A-I, B y A-IV 360. RESULTADOS: La alimentación pobre en grasa y la alimentación mediterránea descendieron significativamente el colesterol total, el colesterol unido a lipoproteínas de baja densidad (cLDL) y colesterol unido a lipoproteínas de alta densidad (cHDL). Los que estaban en el tercil superior de cLDL, tras la SAT, tuvieron mayores descensos en valores absolutos y relativos tanto con la alimentación mediterránea (-32,9 mg/dl tercil superior, -2,7 mg/dl tercil inferior; p < 0,001), como con la HCO (-28,9 mg/dl tercil superior, -5,9 mg/dl tercil inferior; p < 0,001). En el análisis multivariado, la única variable que influía en la modificación del cLDL, tras el paso de una SAT a cualquiera de las hipolipemiantes, fueron los valores de cLDL obtenidos al final de la dieta SAT. La frecuencia alélica de las diferentes apoproteínas no difería en el grupo de hiperrespondedores frente a hiporrespondedores, definidos estos dos grupos por la respuesta al paso de un período SAT a una dieta cualquiera hipolipemiante. CONCLUSIONES: El descenso del cLDL con dietas hipolipemiantes (pobre en grasa o mediterránea) fue más significativo en aquellos con hipercolesterolemia que partían de valores de cLDL más elevados. (AU)