Novel polymorphisms in the 5' region of the LEP gene: association with leptin levels and response to low-calorie diet in human obesity.
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Adult↗
Biomedical subjects
F Fumeron
Publications and source records attributed to F Fumeron.
Hind III polymorphism of the lipoprotein lipase gene and plasma lipid response to low calorie diet.
OBJECTIVE: To assess the effects of a low calorie diet on plasma lipids according to the Hind III polymorphism of the lipoprotein lipase (LPL) gene in overweight patients. DESIGN: Diet intervention study (25% restriction in energy intake during 2.5 months) in relation to genetic factors. SUBJECTS: 115 unrelated patients (77 women and 38 men) recruited on the basis of 120% of ideal body weight. MEASUREMENTS: Body weight, body mass index, blood lipids and lipoproteins, at entry and after 2.5 months, determination of LPL Hind III genotypes. RESULTS: On spontaneous diet, lipid and lipoproteins differed significantly between Hind III genotypes. Homozygous subjects for the presence of the Hind III cutting site, H2H2, had significantly higher plasma and VLDL triglyceride and apolipoprotein B concentrations than subjects carrying H1 allele. H2H2 subjects reduced their VLDL-triglyceride and apolipoprotein B concentrations more than H1 carriers, in such a way that differences in lipid levels according to genotypes were no more significant after diet. The magnitude of the decrease in triglycerides was positively correlated with the initial concentration but, among hypertriglyceridemic subjects, H2H2 still had the largest decrease in plasma and VLDL-triglycerides. CONCLUSION: The genetic variation at the LPL gene locus affects the response of serum lipid levels to caloric restriction. Overweight subjects with the H2H2 genotype of the LPL Hind III polymorphism are predisposed to hypertriglyceridemia but they are good responders to diet in terms of lipid levels.
Adult↗
Polymorphisms of uncoupling protein (UCP) and beta 3 adrenoreceptor genes in obese people submitted to a low calorie diet.
OBJECTIVE: To investigate whether the genetic polymorphisms of the uncoupling protein (UCP) and beta 3 adrenergic receptor (beta 3 AR) were associated with differences of weight loss in obese patients submitted to a low calorie diet. DESIGN: Longitudinal, clinical intervention study of a 25% restriction in energy intake with respect to genotypes. SUBJECTS: 163 patients with a body mass index above 27. MEASUREMENTS: Body weight and body mass index at baseline and after 2.5 months, genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: For the UCP polymorphism, two alleles, 1 and 2 were identified with respective frequencies of 0.27 and 0.73. The allele 1 was associated with lower body weight loss after diet: 4,6,5.7 and 7.1 kg for the 1-1, 1-2 and 2-2 genotypes respectively (P < 0.05). No difference in weight loss was found according to the beta 3 AR Trp64Arg mutation. CONCLUSIONS: A genetic variant of the UCP gene is associated with a resistance to low calorie diet. This result, together with previous data on body weight gain, supports the hypothesis of a role of UCP and brown adipose tissue in the body weight regulation in humans. The importance of the Trp64Arg mutation of the beta 3 AR in the resistance to low calorie diet is still to demonstrate.
Adult↗
Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester transfer protein gene on plasma high density lipoprotein and the risk of myocardial infarction.
A polymorphism of the CETP gene (CETP/TaqIB) with two alleles B1 (60%) and B2 (40%) has been investigated in relation to lipid variables and the risk of myocardial infarction in a large case-control study (ECTIM) of men aged 25-64. No association was observed between the polymorphism and LDL or VLDL related lipid variables. Conversely, B2 carriers had reduced levels of plasma CETP (P < 0.0001) and increased levels of HDL cholesterol (P < 0.0001) and of other HDL related lipid variables. The effects of the polymorphism on plasma CETP and HDL cholesterol were independent, suggesting the presence of at least two functional variants linked to B2. A search for these variants on the coding sequence of the CETP gene failed to identify them. The effect of B2 on plasma HDL cholesterol was absent in subjects drinking < 25 grams/d of alcohol but increased commensurably, with higher values of alcohol consumption (interaction: P < 0.0001). A similar interaction was not observed for plasma CETP. The odds-ratio for myocardial infarction of B2 homozygotes decreased from 1.0 in nondrinkers to 0.34 in those drinking 75 grams/d or more. These results provide the first demonstration of a gene-environment interaction affecting HDL cholesterol levels and coronary heart disease risk.
Adult↗
Lipoprotein lipase gene polymorphisms: associations with hypertriglyceridemia and body mass index in obese people.
OBJECTIVE: To compare body mass index (BMI), lipid, lipoprotein and apolipoprotein concentrations according to the Hind III and Pvu II restriction polymorphisms of the LPL gene in obese subjects. DESIGN: Cross sectional study of anthropometric and lipid variables in relation to genetic factors. SETTING: Nutrition Outpatient Clinic of Bichat Hospital in Paris, France. SUBJECTS: 236 unrelated patients (162 women and 74 men) were selected on the basis of 120% of ideal body weight. MAIN OUTCOME MEASURES: Anthropometry (body mass index, waist to hip ratio), blood lipids and lipoproteins, determination of LPL Hind III and Pvu II genotypes. RESULTS: Digestion with Hind III generated two alleles, H1 (absence of cutting site) and H2 (presence of cutting site), with frequencies of 0.30 and 0.70 respectively. Digestion with Pvu II generated two alleles P1 and P2 with frequencies of 0.49 and 0.51 respectively. The Hind III polymorphism was significantly associated with body mass index (BMI) (P < 0.05). The H2H2 genotype was associated with hypertriglyceridemia: 68% of the hypertriglyceridemic subjects have the H2H2 genotype vs 43% of the normotriglyceridemic group (P < 0.05). Plasma triglyceride levels varied significantly among the Hind III genotypes, H2H2 genotype having the highest total and VLDL-triglyceride levels; the Hind III polymorphism also showed a significant association with HDL2-cholesterol. These associations were only seen in women and were not explained by the variations in BMI and age. No significant associations were found between lipid traits and Pvu II genotype. CONCLUSION: These results suggest that genetic variation in the LPL gene in obese subjects is associated with hypertriglyceridemia and possibly with a predisposition to obesity.
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Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude Cas Témoin sur l'Infarctus du Myocarde.
Several lipoprotein lipase (LPL) gene polymorphisms have been found associated with fasting lipid levels, but their impact on coronary heart disease (CHD) is less clearly established. We investigated associations of LPL polymorphisms (HindIII, PvuII, Ser447-->Ter) and the newly described mutation Asn291-->Ser with the risk of myocardial infarction (MI), severity of atherosclerosis, and fasting plasma lipoprotein concentrations in the ECTIM study (614 patients and 733 controls). The Ter447 allele had a lowering effect on triglycerides (P < 0.01), VLDL-cholesterol (P < 0.05), apoC-III (P < 0.001), LpE:B (P < 0.01), and LpCIII:B (P < 0.05), and a raising effect on apoA-I levels (P < 0.05). The H- allele of the HindIII polymorphism was associated with lower apoC-III (P < 0.01) and higher HDL-cholesterol (P < 0.05) levels. The PvuII and Asn291-->Ser polymorphisms did not exhibit any significant association with the biochemical traits examined. The HindIII genotype distributions differed between cases and controls, the odds ratios for MI associated with H+H+ and H+H- genotypes being 2.05 (P < 0.01) and 1.74 (P < 0.05) by reference to H-H-. The lack of association between Ser447-->Ter and MI suggested that this mutation was unlikely to be the cause of the association found with HindIII. In some cases, the severity of atherosclerosis assessed by coronarography increased with the presence of P+ allele (coronary scores: 1.41, 1.57, and 1.64 in P-P-, P-P+, and P+P+ individuals respectively, P < 0.05). A similar trend on the coronary score was observed with the presence of the Asn291-->Ser mutation (1.58 vs. 1.90, P = 0.06). Our results suggest that the LPL gene is involved in the determination of lipoprotein profiles, the predisposition to CHD, and the severity of atherosclerosis.
Adult↗
Xmn1 restriction polymorphism of apolipoprotein AI gene and lipoprotein levels in obesity.
The aim of this study was to assess any association between an Xmn1 restriction site polymorphism of the apo AI gene and lipoprotein levels in obesity. A cross sectional study was made of lipid variables in relation to genetic and anthropometric factors in obese people at the Nutrition Outpatient Clinic of Bichat Hospital in Paris, France. The subjects were 97 unrelated French Caucasian subjects (65 women and 32 men) selected on the basis of 20% over-weight. The following main outcome measures were recorded: body mass index (BMI) and waist to hip ratio (WHR), cholesterol (C) and triglyceride (TG) concentrations in serum and lipoproteins (including HDL subfractions), apolipoproteins AI and B, determination of apo AI Xmn1 genotypes. Three alleles, designated X1, X2, X3, could be detected with frequencies 0.84, 0.12, and 0.04 respectively. The X2 carriers had higher concentrations of LpA-I, A-II (HDL particles containing both Apo AI and Apo AII) in the whole group: 0.90 vs 0.77 and 0.72 g/l in X1X1 and X1X3 respectively (P < 0.01). The genotype X1X2 was also associated with higher HDL-C in obese men (0.47 vs 0.36 g/l in X1X1, P < 0.05). In X1X1 women, BMI was positively correlated with serum and VLDL-TG (P < 0.05) and negatively with HDL2-C (P < 0.05), WHR being positively correlated with serum TG (P < 0.05), VLDL-TG (P < 0.01) and negatively with HDL-(P < 0.05) and HDL2-C (P < 0.01). These correlations were not found in subjects carrying the X2 allele.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Presence of the French Canadian deletion in a French patient with familial hypercholesterolemia.
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Canada↗
Effect of a moderate alcohol intake on the lipoproteins of normotriglyceridemic obese subjects compared with normoponderal controls.
Moderate alcohol intake is frequently associated with an elevated concentration of high-density lipoprotein (HDL), which is one of the potential causes for the relative decrease in cardiovascular risk reported in moderate drinkers. Conversely, low HDL concentrations, particularly HDL2, in obese subjects may be a risk factor. The effect of 30 g alcohol daily (wine) during 14 days following a period of abstinence was studied in seven normolipidemic obese subjects (body mass index [BMI], 30 +/- 1.7 kg/m2) compared with seven normoponderal controls (BMI, 22 +/- 1.2 kg/m2). Alcohol caused apolipoprotein (apo) AI and apo AII concentrations to increase in all controls by 12% and 16% (P less than .05), but not in obese subjects. Lipoprotein (Lp) AI HDL particles (without AII) were initially in the same proportions in the two groups. Their increase in controls only (P less than .03) was not matched by an increase in HDL2 in all subjects. In obese subjects, neither Lp AI nor HDL2 were increased by alcohol, but their HDL-triglyceride (TG) contents, initially elevated, were normalized. Cholesterol ester (CE) transfer activity was not different in controls and obese subjects during abstinence (105.7 +/- 40.8 v 104.8 +/- 34.5 mmol/mg protein/h). It was notably depressed by alcohol in controls (74.2 +/- 27.4, P less than .002), but not in obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Association of a DNA polymorphism of the apolipoprotein A-I/C-III/A-IV gene cluster with hypertriglyceridemia in obese people.
Hypertriglyceridemia is frequently associated with obesity. In the general Caucasian population, an association of the uncommon S2 allele of a DNA polymorphism of the apolipoprotein (apo) A-I/C-III/A-IV gene cluster with hypertriglyceridemia has been reported. To assess the risk of hypertriglyceridemia associated with the S2 allele in obesity, lipid status and apo A-I/C-III/A-IV genotypes were studied in 90 unrelated Caucasian obese subjects. Age, body mass index, percentage body fat and waist-hip ratio were comparable between genotypes. The frequency of S1/S2 genotype was 35% in the hypertriglyceridemic group versus 11.4% in the normotriglyceridemic group (P < 0.05). The odds ratio of hypertriglyceridemia was 3.7 for obese subjects with the S2 allele and 26.7% of hypertriglyceridemias could be attributed to the S2 allele. Women with the S1/S2 genotype had also significantly higher VLDL- and LDL-cholesterol concentrations. These results suggest that the S2 allele modulates the effects of obesity on lipoproteins and increases the risk of hypertriglyceridemia when obese.
Adult↗
Lack of plasmic beta-endorphin response to a gastronomic meal in healthy humans.
In order to study the relationship between the endogenous opiate system and food intake in man, plasma concentrations of beta-endorphin were measured in ten healthy subjects. Time course of beta-endorphinemia was compared under the following conditions: basal (fasting), after an injection of pentagastrin (6 micrograms/kg), or after a gastronomic meal. No changes in plasma beta-endorphin or ACTH concentrations were observed with pentagastrin nor after the meal, despite the combination of very high sensory pleasure with intake of a very large amount of food. It is concluded that blood beta-endorphin concentration is not a sensitive index of the effects of food intake on the endogenous opioid system in man.
Adult↗
Lowering of HDL2-cholesterol and lipoprotein A-I particle levels by increasing the ratio of polyunsaturated to saturated fatty acids.
The protective role of high-density lipoproteins (HDLs) has been attributed to the subfractions HDL2 (according to the density) and lipoprotein A-I (LpA-I) (according to the composition in apolipoproteins). We investigated the effect of a high ratio of polyunsaturated to saturated fatty acids (P:S) on these subfractions in a homogeneous group of young adult males. Two prescribed diets were consumed successively at the subjects' homes for 3 wk each in a random order; one diet contained 70 g butter (P:S 0.2, diet B), the other contained 70 g sunflower margarine (P:S 1.1, diet M). Total calorie, fat, and cholesterol intakes were similar for the two diets. Cholesterol and apolipoprotein B in serum and in low-density lipoproteins (LDLs) were lower with diet M than with diet B. However, significant decreases in protective subfractions of HDL, HDL2, and LpA-I were observed. This undesirable effect of the diet with a high P:S could cancel the benefits of lowering the LDL-cholesterol concentrations.
Adult↗
n-3 polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men.
The effects of a moderate supplementation in n-3 polyunsaturated fatty acids (PUFAs) were investigated in 36 young healthy adult males. Factors investigated were lipoprotein (including HDL subfractions and apolipoproteins) and hemostasis indexes, assessed by platelet aggregation and plasminogen-activator-inhibitor (PAI) activity. Fat-controlled diets were prescribed, one with and one without a fish-oil supplement (control diet), successively during 3 wk in random order. Total calorie, fat, and cholesterol intakes were similar in the two diets. Triglycerides in serum and very-low-density lipoproteins were lower and high-density-lipoprotein 2 cholesterol was higher with the n-3 PUFA-supplemented diet. These effects as well as a significant decrease in platelet aggregation can be considered beneficial in terms of cardiovascular risk. However, significant increases in low-density-lipoprotein cholesterol and PAI activity occurred and were correlated. This latter effect could be detrimental.
Adult↗
Lack of association between dietary alcohol and HDL-cholesterol concentrations in obese women.
The relationships of alcohol intake and corpulence to HDL-cholesterol were studied in 653 women taking medical advice about body weight. The body mass index (BMI) was positively correlated with triglyceride and negatively with HDL-cholesterol. The relation between BMI and HDL-cholesterol was discontinuous. Total cholesterol, triglycerides and diastolic blood pressure were increased for alcohol intakes greater than 10 g/d regardless of body weight. Alcohol intake was associated with higher concentrations of HDL-cholesterol (P = 0.006) in non obese (BMI = 25.2 +/- 1.5 kg/m2) subjects, but not in mildly (27.3 less than or equal to BMI less than 32.3) or massively (BMI greater than or equal to 32.3) obese subjects. The fact that HDL concentrations were not associated with alcohol intake in obese patients suggests that (1) alcohol acts on the HDL pool through one of the pathways which are perturbed in obesity, possibly lipolysis, (2) obesity is one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol, (3) myocardial infarction might not be inversely correlated with alcohol intake in the obese as it is in the non-obese population.
Adult↗
Iron intake in obese menstruating women.
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Adult↗
Circadian rhythm of energy intake and corpulence status in adults.
The relationship between circadian distribution of energy intake and corpulence was studied in 1312 subjects seeking medical advice for their weight. The corpulence categories (non-obese, mildly obese and massively obese) were defined on the basis of NHANES II. Food consumption was assessed through the dietary history method. The 24 h energy intake increased with corpulence. The lunch represented higher (P less than 0.001) proportions of daily intake in mildly and in massively obese than in non-obese. The reverse occurred for the breakfast (P less than 0.001). The relationships of corpulence with breakfast and lunch persisted after adjustment for nutrient intake. No difference was found for dinner and extra-prandial food intake. Such data suggests several behavioural and/or metabolic hypothesis.
Adult↗
A positive correlation between energy intake and body mass index in a population of 1312 overweight subjects.
The energy intake (EI) of 1312 overweight subjects was assessed using the research dietary history method. EI was positively associated with overweight--as expressed by the body mass index (BMI)--in both males and females. Such findings are at variance with earlier reports of low dietary intakes in the obese and of an inverse relationship between EI and BMI. This discrepancy could be related to the dietary-interviews method used and/or to differences in the degree of motivation of the obese subjects in the various studies. On the other hand, our results are consistent with the positive relationship between energy expenditure (EE) and BMI previously reported in the literature and with the expected EE of our subjects.
Adult↗
Low high density lipoprotein-2 concentrations in obese male subjects.
In this study we have compared the lipoprotein patterns, in particular HDL subfractions, of 34 obese men to those of 34 normoponderal normolipemic men, matched for age and use of tobacco. Obesity was associated with increased VLDL concentrations in only half the subjects. HDL concentrations in all obese subjects were lower than in matched controls. The decrease was most marked in the HDL2 subfraction in which cholesterol and protein contents were decreased by 50%; it was independent of triglyceride levels and not related to the severity of overweight. Moreover, while HDL2 was negatively correlated with BMI (P less than 0.01) when both populations were considered together, the correlation disappeared when calculated separately within each population, suggesting a threshold effect. The low levels of HDL2 might result from discretely altered lipolysis, not sufficient to cause an elevation in fasting triglyceridemia. In this case, HDL2 should prove to be a sensitive index of lipolytic efficiency.
Adult↗