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F Fumeron

Publications and source records attributed to F Fumeron.

At least 19 recordsLinked to original sources
PubMed2005

Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects.

AIMS/HYPOTHESIS: Insulin resistance is related to an increased risk of diabetic retinopathy and nephropathy in type 1 diabetes. Patients with insulin resistance and/or macrovascular disease have abnormally low levels of adiponectin. The aim of this study was to investigate the relationships between adiponectin and renal and retinal diabetic complications in type 1 diabetic patients. METHODS: In this 6-year prospective follow-up observational study, we evaluated the severity of retinopathy at baseline and determined the incident risk of microalbuminuria in 126 normoalbuminuric patients with type 1 diabetes. Each patient was age- and sex-matched to two non-diabetic control subjects. RESULTS: Plasma adiponectin concentrations were significantly higher in diabetic subjects than in control subjects (p < 0.0001). The adiponectin concentration was significantly higher in patients with severe diabetic retinopathy than in those without (39.1+/-14.0 vs 29.0+/-13.0 microg/ml, p = 0.0005). The 18 patients who developed persistent microalbuminuria had higher adiponectin concentrations than the other patients (35.8+/-14.5 vs 30.6+/-13.7 microg/ml). Increased adiponectin concentrations were independently associated with the occurrence of microalbuminuria (p = 0.0158) after adjustment for baseline urinary albumin concentration (p = 0.004), sex (p = 0.0054), blood pressure (NS) and metabolic control (NS). CONCLUSIONS/INTERPRETATION: The elevated adiponectin concentrations observed in subjects with microvascular disease may indicate an altered regulation of this adipocytokine in patients with complications associated with type 1 diabetes.

Adiponectin↗
PubMed2004

Apolipoprotein B signal peptide polymorphism and plasma LDL-cholesterol response to low-calorie diet.

OBJECTIVE: To assess the effect of the apolipoprotein B Ins/Del signal peptide. Polymorphism on plasma lipid levels in overweight subjects before and after a low-calorie diet. DESIGN: Diet intervention study (25% reduction in energy intake during 2.5 months) in relation to genetic factors. SUBJECTS: A total of 231 unrelated patients (146 women/85 men) recruited on the basis of body mass index (BMI)> or =25 kg/m(2). MEASUREMENTS: BMI, waist to hip ratio, blood lipids and lipoproteins, at entry and after 2.5 months, determination of apo B Ins/Del genotypes. RESULTS: On spontaneous diet, subjects carrying the Del allele had higher LDL-cholesterol (Del/Del: 3.97+/-0.62 mmol/l; Ins/Del: 3.87+/-1.01 mmol/l; Ins/Ins: 3.61+/-0.88 mmol/l) (P=0.038). When submitted to low-calorie diet, subjects with Del/Del genotypes reduced their LDL-cholesterol (-16.8%) more than subjects with Ins/Del or Ins/Ins (-4.7% and +0.9%, respectively) (P=0.001). CONCLUSION: In overweight or obese people, the response of plasma LDL-cholesterol levels to low-calorie diet is modulated by genetic variation at the apo B locus. Overweight subjects with the Del allele of the apo B signal peptide polymorphism are predisposed to high LDL cholesterol levels but their LDL cholesterol responds well to diet. These results demonstrate the importance of the interaction between genes and nutritional environment in the determination of the lipid levels.

Adult↗
PubMed2001

Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease.

Coronary atherosclerosis is a major cause of death in industrialized countries. Monocytes, which play a key role in atherosclerosis, migrate into the vessel wall, presumably guided by specific chemoattractant and adhesion molecules. A compelling candidate for this role is the chemokine receptor CX3CR1, which is expressed on monocytes and acts as either a chemotactic receptor or an adhesion molecule, depending on whether its ligand, fractalkine, is presented free or membrane bound. A common variant of CX3CR1 was recently identified, encoded by the alleles I249 and M280, which form a common I(249)M(280) haplotype. When CX3CR1 genotypes were analyzed in 151 patients with acute coronary syndromes and in 249 healthy controls, CX3CR1 I249 heterozygosity was associated with a markedly reduced risk of acute coronary events, independent of established acquired coronary risk factors (eg, smoking, diabetes). The adjusted odds ratio for this allele was 0.43 (95% confidence interval, 0.26-0.72; P =.001). Consistent with this, functional analysis of peripheral blood mononuclear cells showed that CX3CR1 I249 heterozygosity was associated with a significant decrease in the number of fractalkine binding sites per cell. The results show that CX3CR1 I249 is an independent genetic risk factor for coronary artery disease and that CX3CR1 may be involved in the pathogenesis of atherosclerotic disease. (Blood. 2001;97:1925-1928)

Acute Disease↗
PubMed2001

LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women.

BACKGROUND: In humans, a mutation of the leptin receptor gene (LEPR) leads to a rare obese syndrome of mendelian inheritance. However, obesity in humans results from interactions between genes and environment, mainly nutritional factors. Variations at the LEPR locus could be involved in the regulation of body weight. DESIGN: Genetic variations at the LEPR locus were screened in a selection of 30 French overweight subjects by Single Strand Conformation Polymorphism (SSCP) analysis, then an association study between genotypes and obesity phenotypes was performed in 179 French overweight patients recruited from the Nutrition Department of Bichat Hospital in Paris who were prescribed a low calorie diet and in 387 unrelated volunteers (98 overweight, 289 normal weight) drawn from the Stanislas Family Study in Nancy. RESULTS: Two new genetic variants were found: T + 70-->C (exon 1) and Asp (A) 96 Asp (G) (exon 4). In Nancy, the T + 70-->C polymorphism was associated with fat mass adjusted for BMI in women (P = 0.025). The genotype and allele frequencies of the Ser (T) 343 Ser (C) polymorphism (exon 9) were significantly different between normal and overweight women, with the T allele being more frequent in the overweight group (T frequency in Nancy, 0.82; in Nancy + Paris, 0.79) than in the normal weight group (0.69; P = 0.017 vs. Nancy overweight, P = 0.003 vs. Nancy + Paris overweight). In women from Nancy, fat mass adjusted for BMI was significantly associated with this polymorphism (P = 0.01). The overweight women carrying the C allele of this polymorphism lost more weight in response to low calorie diet than the non carriers (P = 0.006). CONCLUSIONS: In women, genetic variations at the LEPR gene level are associated with overweight and fat mass in a cross sectional study and with response to low calorie diet in an intervention study. These results indicate that variations at the leptin receptor locus are associated with common obesity phenotypes and are a part of the polygenic influences on the response to nutritional environment.

Adipose Tissue↗
PubMed2000

Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction.

An extensive association analysis of a candidate gene for coronary heart disease, Cholesteryl Ester Transfer Protein (CETP) gene, was performed. Ten polymorphisms, out of which three were newly identified in regulatory regions, were investigated for association with myocardial infarction (MI) and 2 MI endophenotypes (CETP mass and HDL-cholesterol level) in 568 MI patients and 668 controls. The polymorphisms affecting codon 405 (Ile(405)Val) and the nucleotide 524 downstream from the stop codon (G(+524)T) were almost completely concordant and associated with plasma CETP mass (P < 0.001). The polymorphisms -629 (located in promoter), intron1 (Taq1B) and intron7 were almost completely concordant and associated with plasma CETP mass (P < 0.0001) and HDL-cholesterol levels (P < 0.0001). This latter association was not found in teetotalers and increased with the quantity of alcohol consumed. Heavy drinkers (>75g/day) homozygous for the (-628)A allele had a reduced risk of MI (OR = 0. 33, P < 0.02). Subjects both homozygous for (451)Arg and heterozygous for (373)Pro had decreased plasma HDL-cholesterol levels and this effect increased with alcohol consumption. The results illustrate the complexity of polymorphism-phenotype associations. They suggest that the CETP gene may carry several functional polymorphisms. Observed interactions between alcohol consumption and polymorphisms associated with HDL-cholesterol level constitute concrete examples of gene-environment interactions. Furthermore, the pattern of association between HDL-cholesterol levels and the polymorphisms at codons 373 and 451 illustrated how two polymorphisms may be confounders (in the usual epidemiological sense) one for the other: their marginal effects are neutralized because of linkage disequilibrium and thus are not detectable by standard univariate association analysis.

Adult↗
PubMed2000

Association of the G-2548A polymorphism in the 5' region of the LEP gene with overweight.

Mutations in the translated part of the leptin gene (LEP) have been found in only two families. Nevertheless DNA polymorphisms in the LEP region are linked to extreme obesity. We previously found in the 5' region of LEP a polymorphism, G-2548A, associated with a differerce in BMI reduction following a low calorie diet in overweight women. Recently, this polymorphism was associated with extreme obesity in women. In this work, we genotyped a new sample from the general population including 314 normal weight (BMI < 27 kg/m2) and 109 overweight subjects (BMI > or = 27 kg/m2). The genotype and allele frequencies were significantly different between groups, with the G-2548 allele being more frequent in the overweight subjects (p < 0.01). In men, carriers of this allele had lower leptin concentrations adjusted for fat mass (p = 0.05). Our results indicate that variations at the leptin locus are associated with common obesity phenotypes, and not only with extreme obesity or the rare mendelian obesity syndromes.

Adult↗
PubMed2000

5-HT2A receptor gene polymorphism is associated with food and alcohol intake in obese people.

OBJECTIVE: To test the association between a polymorphism of the 5-HT2A receptor gene, -1438G/A, and energy and nutrients intake, including alcohol. SUBJECTS: Two hundred and seventy six unrelated overweight subjects (180 women, 96 men) were recruited from the Nutrition Department of Bichat Hospital in Paris on the basis of 120% of ideal body weight (body mass index, BMI=33.3+/-4.8 kg/m2). A second overweight sample (31 women, 49 men) was drawn from the Stanislas Family Study, composed of volunteers for a free health examination in Nancy (BMI=29.6+/-3.1 kg/m2). MEASUREMENTS: Energy and nutrients intake were assessed using the diet history method in Paris and the 3-day record method in Nancy. We analyzed the polymorphism by PCR followed by MspI digestion. Statistical differences between genotypes were assessed by using the non-parametric Kruskal-Wallis test. RESULTS: In the whole overweight population, the A allele was associated with lower energy intake 10. 3+/-2.8, 9.9+/-2.8, 9.3+/-2.9 MJ/day for GG, GA and AA genotypes respectively (P<0.05). This association was significant in the patient sample from Paris and in the overweight male volunteers from Nancy. Allele A-related lowering in energy intake was due to a trend to lower intakes in all the main nutrients. The A allele was also associated with a lower alcohol consumption: 18.4+/-19.7, 15.3+/-21. 2 and 12.3+/-17.5 g/day for GG, GA and AA genotypes, respectively (P<0.05). CONCLUSIONS: These data indicate that a gene polymorphism may influence food and alcohol intake in overweight humans. This could be explained by the role of the serotonergic system as a determinant of food intake.

Adult↗
PubMed2000

Beneficial effects of a moderate consumption of red wine on cellular cholesterol efflux in young men.

BACKGROUND AND AIM: Protection against coronary artery disease (CAD) by moderate alcohol consumption is thought to be partly mediated through an increase in high density lipoprotein (HDL) levels. The protective effect of HDL can be related to its role in reverse cholesterol transport. Some studies have shown that wine intake is associated with a lower CAD risk compared to other alcoholic beverages. METHODS AND RESULTS: In order to separate the possible beneficial effects of the alcoholic and the non-alcoholic components of red wine, three beverages were compared in a group of 56 healthy young men: red wine (W) (30 g alcohol/day), a solution with the same degree of alcohol (A) and alcohol-free red wine (AFW). Beverages were consumed in random order over a period of 14 days. W significantly increased serum HDL-C, Apo A-I, HDL3-C, LpA-I and LpA-I:A-II particles. With A, only ApoA-I, HDL3-C, LpA-I:A-II were increased, though triglycerides were also increased. AFW had no effect apart from decreasing HDL-C. Plasma CETP was never altered. Serum-promoted cellular cholesterol efflux was measured on 3H labelled Fu5AH cells. Fractional cholesterol efflux was increased only after W intake, by 7%. Efflux variations correlated positively with HDL-C, HDL3-C and HDL-phospholipid variations. CONCLUSIONS: A modest, specific beneficial effect of moderate red wine consumption was demonstrated in comparison to an alcoholic solution. This was due to its effects on lipoproteins and its stimulation of serum ability to induce efflux of cellular cholesterol.

Adult↗
PubMed2000

A new T-287C polymorphism in the 5' regulatory region of the tissue factor pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels.

Tissue factor pathway inhibitor (TFPI) is an important regulator of the extrinsic blood coagulation pathway. We screened the untranslated 5' region of the TFPI gene for polymorphisms and investigated their possible involvement in arterial thrombosis. The allele frequencies of a new polymorphism, located 287 base pairs upstream of the transcription start site (T-287C), and that of the previously described C-399T polymorphism, were similar in cases and controls. In controls, the -287C allele was associated with significantly higher levels of total TFPI antigen, arguing for an effect of this polymorphism on TFPI gene expression. In controls, the C-399T polymorphism did not alter TFPI levels. In the cases, however, decreased total and post-heparin free TFPI levels and increased F1+2 levels were significantly associated with the -399T allele. These findings suggest that the T-287C and C-399T polymorphisms are not associated with an increased risk of coronary heart disease, a result which should be confirmed by a larger study. However, their influence on outcome, or a link with subtypes of acute coronary syndromes, cannot be excluded.

5' Untranslated Regions↗
PubMed1999

Lack of association between genetic variations of apo A-I-C-III-A-IV gene cluster and myocardial infarction in a sample of European male: ECTIM study.

The goal of the present study was to compare the allele frequency of four polymorphisms at the apo A-I C-III A-IV cluster gene locus-ApoA-I: XmnI and PstI; ApoC-III: SstI; ApoA-IV: XbaI-between male patients who had had a myocardial infarction (n= 614) and matched controls (n = 764). The association with a number of lipid lipoprotein, apolipoprotein and lipoprotein particle variables was also assessed. Patients and subjects were recruited in Belfast, Lille, Strasbourg and Toulouse in the framework of the ECTIM study. In the control group, the frequencies of the different polymorphic alleles were homogeneous among recruitment centres suggesting the absence of any European North to South gradient for these cluster polymorphisms. There was no evidence for a significant difference in allelic distribution between cases and controls suggesting that apo A-I, C-III, A-IV gene cluster polymorphisms do not explain MI survival in this sample of European men. There was no statistically significant association between apo A-I C-III A-IV cluster gene polymorphisms and lipid, lipoprotein, apolipoprotein, and lipoprotein particle levels. In conclusion, in the ECTIM study, the apo A-I, C-III, A-IV gene cluster polymorphism is associated with neither circulating plasma variables nor MI survival.

Adult↗
PubMed1999

Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects : impact of the V264M substitution on plasma levels of TFPI.

-Mutations of the gene encoding tissue factor pathway inhibitor (TFPI), an inhibitor of TF-induced activation of the coagulation cascade, were screened for in 130 patients and 142 healthy controls to determine whether these variants contribute to acute coronary syndromes or modify plasma TFPI levels. The following 3 new polymorphisms were identified: 384T-->C in exon IV, which does not change the corresponding amino acid (tyrosine 57); -33C-->T in intron 7 (the T/T, C/T, and C/C genotypes were found in approximately 50%, 40%, and 10% of subjects in both groups); and 874G-->A in exon IX (GTG-->ATG), which predicts a valine to methionine change (V264M) in the carboxy-terminus tail of TFPI. The V264M polymorphism was found in 9.2% of the cases and 4.9% of the controls; the associated odds ratio (OR) for acute coronary syndromes was 2.0 (95% confidence interval [CI], 0.7 to 5.1). The OR increased to 3.6 (95% CI, 0.8 to 15.7) and 3.2 (95% CI, 0.9 to 11.8) in nonsmokers and patients without other risk factors, respectively. The possible link between the V264M polymorphism and coronary heart disease was checked in a large case-control study of myocardial infarction (Etude Cas-Témoins de l'Infarctus du Myocarde [the ECTIM Study]). The results showed no link between the V264M polymorphism and coronary syndromes. Interestingly, however, 5 patients heterozygous for the V264M polymorphism had significantly lower plasma TFPI levels than did 13 patients with the most common genotype. Although our present results do not support an association between TFPI polymorphisms and acute coronary syndromes, the possibility that 1 of them, especially the exon IX polymorphism, is associated with subtypes of myocardial infarction or to evolutive particularities that were not assessed in this study, cannot be excluded and is currently being evaluated.

Acute Disease↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1995

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↗