Genes, variation of cholesterol and fat intake and serum lipids.

Several studies have examined gene-diet interactions in the response of plasma lipid concentrations to changes in dietary fat and/or cholesterol. Among the gene loci examined, APOE has been the most studied, and the current evidence suggests that this locus might be responsible for some of the interindividual variability in dietary response. Other loci, including APOA4, APOA1 and APOB have also been found to account for some of the variability in the fasting and fed states.

The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle.

The apolipoprotein E4 allele is associated in industrialized countries with an elevated LDL cholesterol concentration and an increased cardiovascular risk. Our purpose in this study was to assess the influence of the genetic variation at the APOE gene locus on the lipid profile of a Native American rural population. We examined plasma lipid levels and the common apo E alleles in 142 healthy randomly selected adults living in their native communities in western Mexico.

Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus.

Previous studies have shown that the A-IV-347Ser polymorphism is associated with the variability in low density lipoprotein (LDL)-cholesterol response to dietary therapy. The present study was designed to evaluate the association of this polymorphism with the individual variability observed in postprandial lipemic response. This polymorphism was characterized in 50 healthy male subjects homozygous for the apolipoprotein (apo)E3 allele.

Frequency of ApoB and ApoE gene mutations as causes of hypobetalipoproteinemia in the framingham offspring population.

Hypobetalipoproteinemia (HBLP) is characterized by plasma concentrations of apolipoprotein B (apoB) and low density lipoprotein cholesterol (LDL-C) below the fifth percentile. Some forms of HBLP have been shown to be due to truncated forms of apoB-100. A total of 3873 subjects participating in the Framingham Offspring Study had LDL-C levels measured every 4 to 5 years throughout a 25-year period.

Effects of different dietary cholesterol concentrations on lipoprotein plasma concentrations and on cholesterol efflux from Fu5AH cells.

Background: The fatty acid composition of the diet can modulate the effect of dietary cholesterol on plasma lipoproteins. However, HDL composition and its capacity to promote cholesterol efflux can be influenced by the diet.

Objective: Modifications in plasma lipids and in the capacity of serum to stimulate the cholesterol efflux induced by a low-fat diet [National Cholesterol Education Program (NCEP) Step I diet], by a monounsaturated fatty acid (MUFA)-rich diet, and by addition of cholesterol to both diets was studied.

Varying dietary fat type of reduced-fat diets has little effect on the susceptibility of LDL to oxidative modification in moderately hypercholesterolemic subjects.

The effect of the fatty acid composition of reduced-fat diets on the in vitro oxidation of LDL was examined in 14 moderately hypercholesterolemic [low density lipoprotein (LDL) > 3.36 mmol/L] postmenopausal female and male subjects (age 44-78 y). Each subject consumed each of five reduced-fat diets [30 energy percent (E%) fat, 17 E% protein and 53 E% carbohydrate] enriched in beef tallow, canola oil, corn oil, olive oil or rice bran oil (20 E%) for 32-d periods.

Genetic variation at the apoA-IV gene locus and response to diet in familial hypercholesterolemia.

Plasma lipid response to dietary fat and cholesterol is, in part, genetically controlled. The apolipoprotein A-IV (apoA-IV protein; APOA4, gene) has been shown to influence the response to dietary changes in normolipidemic individuals. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, and no studies are available on the influence of APOA4 mutations on dietary response in these subjects.

Proposal of a multicompartmental model for use in the study of apolipoprotein E metabolism.

Apolipoprotein (apo) E is a 299-amino acid glycoprotein that serves a number of functions in lipoprotein metabolism. Apo E binds to the triglyceride-rich lipoproteins (TRL), very-low-density lipoprotein (VLDL), and chylomicrons, as they are lipolyzed, mediating their removal from plasma via lipoprotein receptors. Apo E is also found associated with high-density lipoprotein (HDL) and has been suggested to play a role in reverse cholesterol transport.

The SstI polymorphism of the apolipoprotein C-III gene determines the insulin response to an oral-glucose-tolerance test after consumption of a diet rich in saturated fats.

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% saturated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (< 10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrate, 38% fat (22% monounsaturated, < 10% saturated)].

Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia.

We have examined the apo AI - 75 (G/A) and apo AI + 83(MspI +/-) polymorphisms at the APOA1 gene locus for associations with plasma lipid levels and response to an NCEP-I diet in 69 (44 women, 25 men) heterozygotes for familial hypercholesterolemia (FH). Subjects were studied at baseline (after consuming for one month a diet with 35%, fat, 10% saturated, and 300 mg/day cholesterol) and after 3 months of an NCEP-I diet. No gender-related differences for any of the lipid variables examined were found and the data were analyzed for men and women combined.

The effect of quality and amount of dietary fat on the susceptibility of low density lipoprotein to oxidation in subjects with impaired glucose tolerance.

Objectives: We examined the effects of a high fat diet rich in monounsaturated fat (MUFA-diet) and a moderate fat diet rich in polyunsaturated fat (PUFA-diet) on the susceptibility of LDL to oxidation.

Subjects: 29 subjects with impaired glucose tolerance.

Methods: After consuming a run-in diet [37% of energy (E%) fat, 18 E% saturated fat] for three weeks, subjects were randomly assigned either to a MUFA-diet (40 E% fat, 19 E% monounsaturated fatty acids) or a PUFA-diet (34 E% fat, 10 E% polyunsaturated fat) for eight weeks.

The effects of diet and lovastatin on regression of fatty streak lesions and on hepatic and intestinal mRNA levels for the LDL receptor and HMG CoA reductase in F1B hamsters.

This study examined the effects of lovastatin supplementation (25 mg/kg per day) in conjunction with an atherogenic diet (10% coconut oil (w/w), 0.05% cholesterol) on regression of pre-existing foam cells and on hepatic and intestinal LDL receptor and HMG CoA reductase mRNA levels. F1B hamsters fed the atherogenic diet had significantly greater (p < 0.

Beta-glucocerebrosidase gene locus as a link for Gaucher's disease and familial hypo-alpha-lipoproteinaemia.

Background: Gaucher's disease is the most common lysosomal storage disorder, caused by deficiency of glucocerebrosidase resulting from homozygosity for any of several mutations of the glucocerebrosidase gene locus. Affected people have decreased concentrations of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C). We assessed the association between mutations in the glucocerebrosidase locus and hypo-alpha-lipoproteinaemia.

Plasma lipid response to hypolipidemic diets in young healthy non-obese men varies with body mass index.

Lipid response to dietary fat is highly variable among individuals of a population. The aim of this study was to establish whether being overweight is one of the factors that determines this response. Forty-one non-obese healthy men were divided into two groups according to body mass index as follows: controls, <25 kg/m2; overweight, >25 kg/m2 but <30 kg/m2.

Dietary cholesterol affects serum lipids, lipoproteins and LDL metabolism in cynomolgus monkeys in a dose-dependent manner.

To examine the mechanism(s) underlying the cholesterolemic response to dietary cholesterol and saturated fatty acids, low density lipoprotein (LDL) metabolism was studied in two groups of cynomolgus monkeys fed diets containing 30 or 36% of total energy as fat. At each dietary fat level, the same group of monkeys was sequentially fed three dietary cholesterol concentrations as egg yolk in the following sequence: low (0.01 mg/kJ), medium (0.

Remnant lipoprotein cholesterol and triglyceride reference ranges from the Framingham Heart Study.

Remnants of triglyceride-rich lipoproteins of both intestinal and liver origin are considered atherogenic, but they have been difficult to isolate and measure. An assay has been developed that allows the measurement of remnant-like particle cholesterol (RLP-C) and triglyceride (RLP-TG). RLP-C and RLP-TG concentrations were measured in >3000 fasting plasma samples obtained from participants in exam cycle 4 of the Framingham Offspring Study and stored at -80 degrees C.

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days.

Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study.

Background: There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses.

Methods And Results: The study sample consisted of 3095 participants in the Framingham Heart Study.